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Publication numberUS8188277 B2
Publication typeGrant
Application numberUS 11/659,689
Publication dateMay 29, 2012
Filing dateAug 3, 2005
Priority dateAug 6, 2004
Also published asCA2573223A1, CA2573223C, CN1993339A, CN1993339B, EP1773797A2, US20070270422, US20120238750, WO2006014012A2, WO2006014012A3
Publication number11659689, 659689, US 8188277 B2, US 8188277B2, US-B2-8188277, US8188277 B2, US8188277B2
InventorsTae Fukushima, Shuji Matsumura, Noriaki Takemura, Hideaki Satou, Nobuaki Ito, Takuya Shitsuta, Hironori Tsutsui, Michinori Tanaka, Keizo Kan, Hitoshi Nagao, Kenji Watanabe, Kuninori Tai, Takashi Nakagawa, Hideki Takasu, Makoto Sakamoto, Keisuke Miyajima, Satoshi Yamada, Yutaka Kojima, Koichi Yasumura, Naoto Ohi, Mitsuhiro Okuno, Kazuhisa Sugiyama, Kunihiko Kiyono, Takashi Suzuki, Seiji Akamatsu, Takeshi Kodama, Yasuo Yanagihara, Takumi Sumida
Original AssigneeOtsuka Pharmaceutical Co., Ltd.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Aromatic compounds for suppressing the generation of collagen
US 8188277 B2
Abstract
The present invention provides a novel compound, which has an excellent effect of suppressing the generation of collagen and less side effects, with being excellent in terms of safety. The compound of the present invention is represented by the following general formula (1):

[wherein X1 represents a nitrogen atom or a group CH═; R1 represents a group ZR6, wherein Z represents a group CO, a group CH(OH), or the like, and R6 represents a 5- to 15-membered monocyclic, dicyclic, or tricyclic, saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms; R2 represents a hydrogen atom, a halogen atom or a lower alkylene group; Y represents a group O, a group CO, a group CH(OH), a lower alkylene group, or the like; and A represents a group

or the like, wherein R3 represents a hydrogen atom, a lower alkoxy group, or the like, p represents 1 or 2, and R4 represents an imidazolyl lower alkyl group or the like.
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Claims(14)
1. An aromatic compound represented by the general formula (1) or a salt thereof:
[wherein X1 represents a nitrogen atom,
R8 represents a hydrogen atom, a lower alkyl group that may have a lower alkoxy group as a substituent, a lower alkanoyl group, a lower alkylsulfonyl group, or a phenyl lower alkyl group,
B represents a group CO or a lower alkylene group,
R7 represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group that may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group that may have a group, as a substituent, selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group and a cycloalkyl group, a cyano group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkylsulfonyl group, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a lower alkoxycarbonyl lower alkyl group, or a 5- or 6-membered saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (wherein said heterocyclic ring may be substituted by an oxo group),
m represents an integer between 1 and 5, wherein when m represents 2 to 5, two to five R7s may be identical or different,
R2 represents a hydrogen atom, a halogen atom, or a lower alkyl group,
p represents 1 or 2,
R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a group CONR11R12, or a cyano group,
each of R11 and R12, which are identical or different, represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group; or R11 and R12, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, a sulfur atom, or an oxygen atom to form a 5- to 7-membered saturated heterocyclic ring,
T represents a lower alkylene group, a group N(R17)B3CO, a group B19N(R18)CO, a group B4CO, a group -Q-B5CO, a group B6N(R19)B7CO, a group COB8, a group CH(OH)B9, a group COB10CO, a group CH(OH)B11CO, a group CO, a group SO2, or a group B23aCOCO,
R17 represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkenyl group, an amino-substituted lower alkanoyl group that may have a lower alkyl group as a substituent, or a lower alkylsulfonyl group,
B3 represents a lower alkylene group,
B19 represents a lower alkylene group,
R18 represents a hydrogen atom or a lower alkyl group,
B4 represents a lower alkenylene group, or a lower alkylene group that may have a hydroxyl group as a substituent,
Q represents an oxygen atom or a group S(O)n- (wherein n has the same meaning as described above),
B5 represents a lower alkylene group,
B6 represents a lower alkylene group,
R19 represents a hydrogen atom or a lower alkanoyl group,
B7 represents a lower alkylene group,
B8 represents a lower alkylene group,
B9 represents a lower alkylene group,
B10 represents a lower alkylene group,
B11 represents a lower alkylene group,
B23a represents a lower alkylene group,
l represents 0 or 1,
R14 and R15, together with the nitrogen atom to which they bind, form a piperidinyl group or a piperazinyl group, wherein a substituent on the piperidinyl group or the piperazinyl group represents a phenyl-substituted lower alkyl group, which may have a pyridyl group on the lower alkyl group, having 1 to 2 phenyl groups that may be substituted by 1 to 3 groups, as substituent on the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group that may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group].
2. The aromatic compound or a salt thereof according to claim 1, wherein R14 and R15 in the general formula (1), together with the nitrogen atom to which they bind, form a piperidinyl group.
3. The aromatic compound or a salt thereof according to claim 2, wherein l in the general formula (1) represents 1, and T represents a group N(R17)B3CO.
4. The aromatic compound or a salt thereof according to claim 2, wherein l in the general formula (1) represents 1, and T represents a group B4CO.
5. The aromatic compound or a salt thereof according to claim 2, wherein l in the general formula (1) represents 1, and T represents a group CO.
6. The aromatic compound or a salt thereof according to claim 2, wherein l in the general formula (1) represents 0.
7. The aromatic compound or a salt thereof according to claim 1, wherein R14 and R15 in the general formula (1), together with the nitrogen atom to which they bind, form a piperazinyl group.
8. The aromatic compound or a salt thereof according to claim 7, wherein l in the general formula (1) represents 1, and T represents a group N(R17)B3CO.
9. The aromatic compound or a salt thereof according to claim 7, wherein l in the general formula (1) represents 1, and T represents a group B4CO.
10. The aromatic compound or a salt thereof according to claim 7, wherein l in the general formula (1) represents 1, and T represents a group CO.
11. The aromatic compound or a salt thereof according to claim 7, wherein l in the general formula (1) represents 0.
12. The aromatic compound or a salt thereof according to any one of claims 8 to 11, wherein R14 and R15 in the general formula (1), together with the nitrogen atom to which they bind, form a piperonyl group-substituted or benzyl group-substituted piperazinyl group.
13. The aromatic compound or a salt thereof according to claim 1, wherein R7 in the general formula (1) represents a halogen atom, or a lower alkyl group that may have a halogen atom as a substituent, m represents 1 or 2, R8 represents a hydrogen atom, B represents a group CO, R2 represents a hydrogen atom, X1 represents a nitrogen atom, R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, or a lower alkyl group that may have a halogen atom as a substituent, T represents a group N(R17)B3CO, a group B4CO, or a group CO, R17 represents a hydrogen atom or a lower alkyl group, and B4 represents a lower alkylene group.
14. The aromatic compound or a salt thereof according to claim 1, wherein the aromatic compound represented by the general formula (1) is an aromatic compound selected from the group consisting of:
(1) N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methoxyphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
(2) N-{2-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]-2-oxoethyl}-N-{4-[(5-{methyl[4-(trifluoromethyl)benzyl]amino}pyridin-2-yl)oxy]phenyl}acetamide,
(3) N-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide,
(4) N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
(5) N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, and
(6) N-[6-(4-{[4-(4-pivaloylbenzyl)piperazin-1-yl]oxomethyl}phenoxy)pyridin-3-yl]-3,4-dichlorobenzamide.
Description
TECHNICAL FIELD

The present invention relates to an aromatic compound.

BACKGROUND ART

Currently, it is said that the disease known as fibrosis includes 130 types or more of diseases, if rare diseases are also included therein. Representative examples of such fibrosis include lung fibrosis, hepatic fibrosis, and glomerulosclerosis.

In general, lung fibrosis refers to a group of diseases associated with loss of lung functions due to a lesion regarding the reconstruction of an alveolar region, which is caused by the phenomenon whereby the alveolar structure is destroyed by an inflammatory reaction, and as a result, growth of fibroblasts and an excessive increase in extracellular matrix mainly composed of collagen take place, so that the lung becomes hardened.

Moreover, hepatic fibrosis refers to a pathologic condition associated with fibrosis of the liver, which is caused by the phenomenon whereby hepatic cells are necrotized by various types of hepatopathy such as chronic viral hepatitis or alcoholic hepatitis, and thereafter, extracellular matrix increases to replenish the necrotized portion, resulting in such fibrosis of the liver. This pathologic condition finally leads to hepatic cirrhosis, in which the entire hepatic fibers shrink and become hardened.

In order to suppress the aforementioned hepatic fibrosis, drugs such as Penicillamine or Lufironil have been used. Penicillamine has been known as a drug for treating Wilkinson's disease that is developed as a result of accumulation of copper in the liver due to abnormality of copper metabolism. Lufironil has been studied for its use as a proline hydroxylase inhibitor.

However, taking into consideration their side effects and effectiveness, the aforementioned drugs do not sufficiently function as drugs for preventing fibrosis of the liver. Thus, as a matter of fact, neither therapeutic agents nor methods for treating fibrosis, which are effective for fibrosis, including hepatic fibrosis as a representative example, have been established to date. A method of specifically inhibiting a process of developing fibrosis has become a focus of attention in the research field.

As stated above, it has been known that an excessive increase in extracellular matrix mainly composed of collagen takes place during a process of development of fibrosis in the lung tissues or hepatic tissues. Moreover, it has also been known that such an increase in extracellular matrix in hepatic cells takes place mainly in sinusoidal wall Disse's space, and that Ito cells that are mesenchymal cells in the liver are main sources for production of such extracellular matrix.

Accordingly, in order to suppress fibrosis occurring in the liver, the lung, or other organs, it is important to suppress an excessive increase in extracellular matrix (namely, collagen).

JP-A-2002-507601 and JP-A-2001-89450 disclose that a certain type of pyridine derivative has an effect of suppressing the generation of collagen and thus is effective for fibrosis. JP-A-2001-89412 discloses that a certain type of benzene derivative has an effect of suppressing the production of collagen and thus is effective for fibrosis.

However, the effect of suppressing the generation of collagen of the compounds described in JP-A-2002-507601, JP-A-2001-89450, and JP-A-2001-89412 are insufficient, or these compounds have serious side effects. Accordingly, it has strongly been desired that a compound, which has a superior effect of suppressing the production of collagen, less side effects, and excellent safety, will be developed.

DISCLOSURE OF THE INVENTION

It is an object of the present invention to provide a novel compound, which has a superior effect of suppressing the generation of collagen, for example, a pharmaceutical composition being useful for preventing and treating fibrosis such as lung fibrosis, hepatic fibrosis, glomerulosclerosis and the like, with less side effects, and excellent safety.

As a result of intensive studies directed towards achieving the aforementioned object, the present inventors have found that an aromatic compound represented by the following general formula (1) and a salt thereof have a superior effect of suppressing the generation of collagen, less side effects, and excellent safety. The present invention has been completed based on these findings.

The present invention provides an aromatic compound represented by the general formula (1) or a salt thereof:


[wherein X1 represents a nitrogen atom or a group CH═,
R1 represents a group ZR6,
Z represents a group N(R8)B, a group BN(R8), a group B0O, a group


a group CO, a group CH(OH), a group


a group N═CH, a group


a lower alkenylene group, a group NHCOB1, a group NHCOB2(W)u-, a group B0OB19a, a group


a group


a group


a group S, a lower alkynylene group, a lower alkylene group, a group


or a group CONHB18a-,
wherein R8 represents a hydrogen atom, a lower alkyl group that may have a lower alkoxy group as a substituent, a lower alkanoyl group, a phenyl lower alkyl group, or a lower alkylsulfonyl group,
B represents a group CO or a lower alkylene group,
B0 represents a lower alkylene group,
each of R9a and R9b, which are identical or different, represents a hydrogen atom or a lower alkyl group
R10a represents a hydrogen atom or a lower alkyl group,
B22a represents a lower alkylene group or a lower alkenylene group,
e represents 0 or 1,
B1 represents a lower alkenylene group that may have a phenyl group as a substituent,
B2 represents a lower alkylene group that may be substituted by a group selected from the group consisting of a lower alkoxy group and a phenyl group,
W represents an oxygen atom, a group NH, or a sulfur atom,
u represents 0 or 1,
B18a represents a lower alkylene group,
B19a represents a lower alkylene group,
B20a represents a lower alkylene group,
B21a represents a lower alkylene group,
R8d represents a hydrogen atom or a lower alkyl group,
k represents 2 or 3,
c represents 0 or 1,
d′ represents 0 or 1,
R10b represents a hydrogen atom or a lower alkyl group,
R6 represents a 5- to 15-membered monocyclic, dicyclic, or tricyclic saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (wherein, the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of an oxo group; an optionally halogenated lower alkoxy group; an optionally halogenated lower alkyl group; a halogen atom; a lower alkylsulfonyl group; a phenyl group that may be substituted, on the phenyl ring, by an optionally halogenated lower alkyl group; a lower alkylthio group; a pyrrolyl group; a benzoyl group; a lower alkanoyl group; a lower alkoxycarbonyl group; and an amino group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent), an adamantyl group, a naphthyl group (wherein, the naphthalene ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkyl group, a halogen atom, and an amino group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent), an alkyl group that may have a lower alkoxy group as a substituent, a cycloalkyl group that may be substituted, on the cycloalkyl ring, by a group selected from the group consisting of an amino-substituted lower alkyl group that may have a lower alkyl group on the amino group and a lower alkyl group that may have a halogen atom as a substituent, a lower alkenyl group that may have a halogen atom as a substituent, a lower alkanoyl group, a benzoyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group that may have a halogen atom as a substituent and a halogen atom, a group


a halogen atom-substituted lower alkyl group, or a cycloalkyl lower alkyl group,
R7 represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group that may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group that may have, as a substituent, a group selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group, and a cycloalkyl group, a cyano group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkylsulfonyl group, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a 5- or 6-membered saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (wherein the heterocyclic ring may be substituted, by an oxo group), or a lower alkoxycarbonyl lower alkyl group,
m represents an integer between 1 and 5, wherein when m represents 2 to 5, two to five R7s may be identical or different,
R2 represents a hydrogen atom, a halogen atom, or a lower alkyl group,
Y represents a group O, a group N(R5), a group CO, a group CH(OH), a lower alkylene group, a group S(O)n-, or a group C(═NOH),
R5 represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a benzoyl group, a phenyl lower alkyl group, or a cycloalkyl group,
n represents 0, 1, or 2,
A represents a group


or a group


p represents 1 or 2,
R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a group CONR11R12, or a cyano group,
wherein each of R11 and R12, which are identical or different, represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group, or R11 and R12, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring,
R4 represents an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group that may have an oxo group as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group that may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a group


a group


or a group -(T)1-N(R14)R15,
R13 represents a hydrogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a benzoyl group, a morpholino-substituted lower alkanoyl group, a piperazinyl carbonyl lower alkyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, a piperazinyl lower alkanoyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, a morpholinocarbonyl-substituted lower alkyl group, or an imidazolyl lower alkanoyl group,
R13a represents a hydrogen atom or a hydroxyl group,
T represents a lower alkylene group, a group N(R17)B3CO, a group B19N(R18)CO, a group B4CO, a group -Q-B5CO, a group B6N(R19)B7CO, a group COB8, a group CH(OH)B9, a group COB10CO, a group CH(OH)B11CO, a group CO, a group SO2, or a group B23aCOCO,
wherein R17 represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkenyl group, an amino-substituted lower alkanoyl group that may have a lower alkyl group as a substituent, or a lower alkylsulfonyl group,
B3 represents a lower alkylene group,
B19 represents a lower alkylene group,
R18 represents a hydrogen atom or a lower alkyl group,
B4 represents a lower alkenylene group or a lower alkylene group that may have a hydroxyl group as a substituent,
Q represents an oxygen atom or a group S(O)n- (wherein
n has the same meanings as described above),
B5 represents a lower alkylene group,
B6 represents a lower alkylene group,
R19 represents a hydrogen atom or a lower alkanoyl group,
B7 represents a lower alkylene group,
B8 represents a lower alkylene group,
B9 represents a lower alkylene group,
B10 represents a lower alkylene group,
B11 represents a lower alkylene group,
B23a represents a lower alkylene group,
l represents 0 or 1,
R14 represents a hydrogen atom or an alkyl group that may have a hydroxyl group as a substituent,
R15 represents (2) a hydroxyl group-substituted alkyl group, (3) a cycloalkyl group that may have a group selected from the group consisting of a hydroxyl group and a lower alkyl group as a substituent, (4) a phenoxy lower alkyl group, (5) a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group that may have a halogen atom as a substituent; a halogen atom; an amino lower alkoxy group that may have a lower alkyl group as a substituent; a hydroxyl group-substituted lower alkyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group that may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group that may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group that may have a lower alkyl group as a substituent on the piperazine ring; a pyrrolidinyl group that may have an oxo group as a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group, (6) a phenoxy group, (7) a phenyl lower alkyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group that may have a halogen atom as a substituent, and a lower alkyl group, (8) a phenyl lower alkyl group that has a lower alkylenedioxy group as a substituent on the phenyl ring, (10) a lower alkoxycarbonyl-substituted lower alkyl group, (11) a carboxy-substituted lower alkyl group, (12) an amino group that may have a lower alkanoyl group as a substituent, (13) a 1,2,3,4-tetrahydroquinolyl group that may have 1 to 3 groups selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group as a substituent(s) on the tetrahydroquinoline ring, (14) a cycloalkyl lower alkyl group, (15) a piperazinyl lower alkanoyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (16) a pyridyl Lower alkyl group, (17) an amino group-substituted lower alkyl group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, (18) a lower alkoxy lower alkyl group, (19) an imidazolyl group, (20) an imidazolyl lower alkyl group, (21) a 1,2,3,4-tetrahydroisoquinolyl-carbonyl-substituted lower alkyl group, (22) a piperidinylcarbonyl group that may have a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, and a furyl lower alkyl group as a substituent on the piperidine ring, (23) a thiazolidinyl lower alkanoyl group that may have an oxo group as a substituent on the thiazolidine ring, (24) a piperidinyl group that may be substituted, on the piperidine ring, by a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group, and a furyl lower alkyl group, (25) a carbonyl lower alkyl group substituted by a group


, (26) a carbonyl lower alkyl group substituted by a group


(27) a group COB20N(R36)R37, (26a) a pyrrolidinyl lower alkyl group, (27a) a morpholino lower alkyl group, (28a) a phenyl lower alkenyl group, (29a) an anilinocarbonyl lower alkyl group that may have a lower alkyl group as a substituent on the phenyl ring, (30a) an indolyl group, (31a) a piperazinyl lower alkyl group that may have, as a substituent on the piperazine ring, a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (32a) an amidino lower alkyl group that may have a lower alkyl group as a substituent, (33a) a fluorenyl group, (34a) a carbazolyl group that may have a lower alkyl group as a substituent on the carbazole ring, (35a) an amidino group that may have a lower alkyl group as a substituent, (36a) a piperazinyl-substituted oxalyl group that may have 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group as a substituent(s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent(s) on the piperazine ring, or (37a) a cyano-substituted lower alkyl group,
R34 represents an oxo group or a phenyl group,
d represents an integer between 0 and 3,
B20 represents a lower alkylene group,
R36 and R37, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein the heterocyclic group may be substituted by 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
R14 and R15, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated or unsaturated heterocyclic ring; or a group


wherein the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of (28) a phenyl-substituted lower alkyl group, which has 1 to 2 phenyl groups and which may have a pyridyl group on the lower alkyl group, wherein the phenyl ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkanoyl group, an amino group that may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group, (29) a carbamoyl group, (30) a pyridyl lower alkyl group that may have, as a substituent(s) on the pyridine ring, 1 to 3 groups selected from the group consisting of a hydroxyl group and a lower alkyl group that may have a hydroxyl group as a substituent, (31) a pyrrolyl lower alkyl group that may have 1 to 3 lower alkyl groups as a substituent(s) on the pyrrole ring, (32) a benzoxazolyl lower alkyl group, (33) a benzothiazolyl lower alkyl group, (34) a furyl lower alkyl group, (35) a benzoyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, an amino group that may have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group that may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group, (36) a pyrimidinyl group, (37) a pyrazinyl group, (38) a pyridyl group, (39) a lower alkoxycarbonyl group, (40) a thiazolidinyl lower alkanoyl group that may be substituted, on the thiazolidine ring, by a group selected from the group consisting of an oxo group and a group


(wherein each of Ra and Rb represents a lower alkyl group), (41) a lower alkyl group that may have a group selected from the group consisting of a hydroxyl group and a halogen atom as a substituent, (42) a lower alkanoyl group that may have a halogen atom as a substituent, (43) a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a carbamoyl group that may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a benzoyl group that may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group that may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group, (44) a phenyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (45) a naphthyl lower alkyl group, (46) a phenoxy group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group that may have a halogen atom as a substituent, and a lower alkoxy group that may have a halogen atom as a substituent, (47) a phenoxy lower alkyl group, (48) a phenyl lower alkoxy group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, and a lower alkoxy group that may have a halogen atom as a substituent, (49) a group (B12CO)t-N(R20)R21, (50) a group (CO)o-B13N(R22)R23, (51) a 1,2,3,4-tetrahydronaphthyl-substituted lower alkyl group that may be substituted, on the 1,2,3,4-tetrahydronaphthalene ring, by 1 to 5 lower alkyl groups as a substituent(s), (52) a cycloalkyl group that may have a hydroxyl group as a substituent, (53) a piperidinyl group that may be substituted, on the piperidine ring, by 1 to 3 lower alkyl groups as a substituent(s), (54) a quinolyl lower alkyl group, (55) a 1,2,3,4-tetrazolyl lower alkyl group that may have a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent on the tetrazole ring, (56) a thiazolyl lower alkyl group that may have a phenyl group as a substituent on the thiazole ring, (57) a benzoyl lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkoxy group and a halogen atom as a substituent(s) on the phenyl ring, (58) a piperidinyl lower alkyl group that may have a lower alkyl group as a substituent on the piperidine ring, (59) an imidazolyl group that may have 1 to 3 phenyl groups as a substituent(s) on the imidazole ring, (60) a benzimidazolyl group that may have 1 to 3 lower alkyl groups as a substituent(s) on the benzimidazole ring, (61) a pyridyl lower alkoxy group, (62) a 1,2,3,4-tetrahydroquinolyl lower alkyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring, (63) a 1,3,4-oxadiazolyl lower alkyl group that may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, (64) a cycloalkyl lower alkyl group, (65) a tetrahydropyranyl group, (66) a thienyl lower alkyl group, (67) a pyrimidinylcarbonyl group that may have an oxo group as a substituent on the pyrimidine ring, (68) a hydroxyl group, (69) a carboxy group, (70) a lower alkoxy lower alkyl group, (71) a lower alkoxy lower alkoxy group, (72) a benzoyloxy group, (73) a lower alkoxycarbonyl lower alkoxy group, (74) a carboxy lower alkoxy group, (75) a phenoxy lower alkanoyl group, (76) a 1,2,3,4-tetrahydroquinolylcarbonyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring, (77) a phenylsulfonyl group, (78) an imidazolyl lower alkanoyl group, (79) an imidazolyl lower alkyl group, (80) a pyridylcarbonyl group, (81) an imidazolylcarbonyl group, (82) a lower alkoxycarbonyl lower alkyl group, (83) a carboxy lower alkyl group, (84) a group (OB15)s-CON(R26)R27, (85) a group N(R28)COB16N(R29)R30, (86) a group N(R31)B17CON(R32)R33 (87) a benzoxazolyl group, (88a) a benzothienyl group, (89a) an oxo group, and (90a) a 1,2,3,4-tetrahydroquinolyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring,
B12 represents a lower alkylene group,
t represents 0 or 1,
each of R20 and R21, which are identical or different, represents a hydrogen atom; a cycloalkyl group; an amino group that may have a lower alkoxycarbonyl group as a substituent; a benzoyl group that may have 1 to 3 lower alkoxy groups as a substituent(s) on the phenyl ring; a lower alkyl group; a lower alkyl group having 1 to 2 phenyl groups that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, and a lower alkylthio group; a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxy group that may have a halogen atom as a substituent and a lower alkyl group that may have a halogen atom as a substituent; a lower alkoxycarbonyl group; a cycloalkyl lower alkyl group; a pyrrolidinyl lower alkyl group that may have 1 to 3 lower alkyl groups that may have a hydroxyl group as a substituent on the pyrrolidine ring; an amino-substituted lower alkyl group that may have a group selected from the group consisting of a phenyl group and a lower alkyl group as a substituent; a 1,2,3,4-tetrahydronaphthyl-substituted lower alkyl group that may have 1 to 5 lower alkyl groups as a substituent(s) on the 1,2,3,4-tetrahydronaphthalene ring; a naphthyl lower alkyl group; a pyridyl lower alkyl group; a quinolyl lower alkyl group; a 1,2,3,4-tetrazolyl lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent(s) on the tetrazole ring; a 1,2,4-triazolyl lower alkyl group; a tetrahydrofuryl lower alkyl group that may have a hydroxyl group as a substituent on the lower alkyl group; a phenoxy lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a nitro group as a substituent(s) on the phenyl ring; a phenyl lower alkanoyl group; a lower alkanoyl group that may have a halogen atom as a substituent; an imidazolyl lower alkanoyl group; a lower alkoxycarbonyl lower alkyl group; a pyridyl group; or a carboxy lower alkyl group, or R20 and R21, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring, wherein the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkyl group, a phenyl group that may have 1 to 3 groups selected from the group consisting of a halogen atom and a lower alkyl group that may have a halogen atom as a substituent(s) on the phenyl ring, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
o represents 0 or 1,
B13 represents a lower alkylene group,
each of R22 and R23, which are identical or different, represents a hydrogen atom, a lower alkyl group, a benzoyl group that may have 1 to 3 lower alkoxy groups as a substituent(s) on the phenyl ring, a phenoxy lower alkyl group that may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group, or a phenyl group, or R22 and R23, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring, wherein the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
B15 represents a lower alkylene group,
s represents 0 or 1,
each of R26 and R27, which are identical or different, represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or an imidazolyl lower alkyl group, or R26 and R27, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring, wherein the heterocyclic ring may be substituted by 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group as a substituent on the phenyl ring, as a substituent(s),
R28 represents a hydrogen atom or a lower alkyl group,
B16 represents a lower alkylene group,
R29 and R30, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
R31 represents a hydrogen atom or a lower alkyl group,
B17 represents a lower alkylene group,
R32 and R33, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
provided that the above described aromatic compound or a salt thereof satisfy the following requirements (i) to (v):

(i) when X1 represents a group CH═, then R3 represents a hydrogen atom;

(ii) when X1 represents a group CH═, l represents 1, T represents CO, and R14 represents a hydrogen atom or an alkyl group that may have a hydroxyl group as a substituent, then R15 represents the group (24) described above;

(iii) when X1 represents a group CH═, 8 represents 1, and T represents N(R17)B3CO, then R14 and R15, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated or unsaturated heterocyclic ring, wherein the heterocyclic ring is substituted by 1 to 3 groups of (28) described above;

(iv) when X1 represents a nitrogen atom, and l represents 0, or when X1 represents a nitrogen atom, l represents 1, and T represents CO or SO2, then R15 is not the group being any one of (5), (7), (19), and (20) described above; and

(v) when R6 represents a cycloalkyl group wherein the cycloalkyl ring may be substituted by a group selected from the group consisting of an amino-substituted lower alkyl group that may have a lower alkyl group and a lower alkyl group that may have a halogen atom as a substituent, then R14 represents a group -(T)l-N(R14)R15 (wherein T and l have the same meanings as described above, and R14 and R15, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated heterocyclic ring; or R14 and R15 form a group)].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds or salts thereof represented by the general formulas (1-1) to (1-7):


[wherein, in said general formulas (1-1) to (1-7), R6, B, R8, R2, R5, n, X1, and A have the same meanings as described above, and Y3 represents a lower alkylene group].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds or salts thereof represented by the general formulas (1-8) to (1-14):


[wherein, in said general formulas (1-8) to (1-14), R6, B, R8, R2, R5, n, X1, A and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds or salts thereof represented by the general formulas (1-15) to (1-21):


[wherein, in said general formulas (1-15) to (1-21), R6, B0, R2, R5, n, X1, A and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds or salts thereof represented by the general formulas (1-22) to (1-28):


[wherein, in said general formulas (1-22) to (1-28), R6, R2, R5, n, X1, A and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds or salts thereof represented by the general formulas (1-29) to (1-35):


[wherein, in said general formulas (1-29) to (1-35), R6, R2, R5, n, X1, A and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds or salts thereof represented by the general formulas (1-36) to (1-42):


[wherein, in said general formulas (1-36) to (1-42), R6, R2, R5, n, X1, A and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds or salts thereof represented by the general formulas (1-43) to (1-49):


[wherein, in said general formulas (1-43) to (1-49), R6, R2, R5, n, X1, A, R9a, R9b and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds or salts thereof represented by the general formulas (1-50) to (1-56):


[wherein, in said general formulas (1-50) to (1-56), R6, R2, R5, n, X1, A and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds or salts thereof represented by the general formulas (1-57) to (1-63):


[wherein, in said general formulas (1-57) to (1-63), R6, R2, R5, n, X1, A, R10a, B22a, e and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds represented by the general formulas (1-64) to (1-70) or salts thereof:


[wherein, in said general formulas (1-64) to (1-70), R6, R2, R5, n, X1, A and Y3 have the same meanings as described above, and Z1 represents a lower alkenylene group].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds represented by the general formulas (1-71) to (1-77) or salts thereof:


[wherein, in said general formulas (1-71) to (1-77), R6, R25, B1, R5, n, X1, A and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds represented by the general formulas (1-78) to (1-84) or salts thereof:


[wherein, in said general formulas (1-78) to (1-84), R6, W, u, B2, R2, R5, n, X1, A and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds represented by the general formulas (1-85) to (1-91) or salts thereof:


[wherein, in said general formulas (1-85) to (1-91), R5, R6, B19a, B0, R2, X1, n, A and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds represented by the general formulas (1-92) to (1-98) or salts thereof:


[wherein, in said general formulas (1-92) to (1-98), R5, R6, B20a, R2, X1, A, n, d′, k and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds represented by the general formulas (1-99) to (1-105) or salts thereof:


[wherein, in said general formulas (1-99) to (1-105), R6, R5, B21a, R2, X1, A, n, c and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds represented by the general formulas (1-106) to (1-112) or salts thereof:


[wherein, in said general formulas (1-106) to (1-112), R5, n, R5, R6, X1, R2, A and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds represented by the general formulas (1-113) to (1-119) or salts thereof:


[wherein, in said general formulas (1-113) to (1-119), R6, R2, X1, R5, n, A and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds represented by the general formulas (1-120) to (1-126) or salts thereof:


[wherein, in said general formulas (1-120) to (1-126), R6, R2, X1, A, R5, n and Y3 have the same meanings as described above, and Z2 represents a lower alkynylene group].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds represented by the general formulas (1-127) to (1-133) or salts thereof:


[wherein, in said general formulas (1-127) to (1-133), R6, B18a, R2, X1, A, R5, n and Y3 have the same meanings as described above].

The above aromatic compound represented by the general formula (1) or a salt thereof includes the following aromatic compounds represented by the general formulas (1-134) to (1-140) or salts thereof:


[wherein, in said general formulas (1-134) to (1-140), R6, R2, X1, A, R5, and n have the same meanings as described in claim 1, Y3 has the same meanings as described in claim 2, and Z3 represents a lower alkylene group or a group


(R8d is the same meanings as described above)].

The present invention provides the above-mentioned aromatic compound or salt thereof wherein Y is a group O.

The present invention provides the above-mentioned aromatic compound or salt thereof wherein Y is a group N(R5) (R5 has the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein Y is a group CO, a group CH(OH), a lower alkylene group, a group S(O)n- (n has the same meanings as described above), or a group C(═NOH).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein A is a group


(R3, R4 and p have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein A is a group


(R4 has the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group that may have an oxo group as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group that may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a group


or a group


(R13 and R13a have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15 (T, R14 and R15 have the same meanings as described above), and l is 0.

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15 (T, R14 and R15 have the same meanings as described above), and l is 1.

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group N(R17)B3CO (R14, R15, R17 and B3 have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group B19N(R18)CO (R14, R15, B19 and R18 have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group B4CO (R14, R15, and B4 have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group -Q-B5CO (R14, R15, Q and B5 have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group B6N(R19)B7 (R14, R15, B6, R19 and B7 have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group COB8 (R14, R15, and B8 have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group CH(OH)B9 (R14, R15, and Bg have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group COB10CO (R14, R15, and B10 have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group CH(OH)B11CO (R14, R15, and B11 have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group CO (R14 and R15 have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group SO2 (R14 and R15 have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a group B23aCOCO (R14, R15 and B23a have the same meanings as described above).

The present invention provides the above-mentioned aromatic compound or salt thereof wherein R4 is a group -(T)l-N(R14)R15, l is 1, and T is a lower alkylene group (R14 and R15 have the same meanings as described above).

In the above-mentioned aromatic compound represented by the general formula (1) or salt thereof, the aromatic compounds represented by the general formulas (1-1), (1-2), (1-8), (1-9), (1-15), (1-16), (1-29), (1-30), (1-64) and (1-65) or salts thereof are preferable.

Further, those compounds represented by the general formulas (1-1), (1-2), (1-8), (1-9), (1-15), (1-16), (1-29), (1-30), (1-43), (1-44), (1-57), (1-58), (1-64) and (1-65) or salts thereof, wherein Y is a group O or a group N(R5), A is a group


, and R4 is a group -(T)l-N(R14) R15 (R3, R4, R5, R14, R15, p and l have the same meanings as described above). are more preferable.

The present invention provides the aromatic compounds represented by the general formulas (1-1), (1-2), (1-8), (1-9), (1-15), (1-16), (1-29), (1-30), (1-43), (1-44), (1-57), (1-58), (1-64) and (1-65) or salts thereof, wherein

l is 1, and T is a group N(R17)B3CO (R17 and B3 have the same meanings as described above).

The present invention provides the aromatic compounds represented by the general formulas (1-1), (1-2), (1-8), (1-9), (1-15), (1-16), (1-29), (1-30), (1-43), (1-44), (1-57), (1-58), (1-64) and (1-65) or salts thereof, wherein

l is 1, and T is a group B4CO (B4 have the same meanings as described above).

The present invention provides the aromatic compounds represented by the general formulas (1-1), (1-2), (1-8), (1-9), (1-15), (1-16), (1-29), (1-30), (1-43), (1-44), (1-57), (1-58), (1-64) and (1-65) or salts thereof, wherein

l is 1, and T is a group CO.

The present invention provides the aromatic compounds represented by the general formulas (1-1), (1-2), (1-8), (1-9), (1-15), (1-16), (1-29), (1-30), (1-43), (1-44), (1-57), (1-58), (1-64) and (1-65) or salts thereof, wherein

l is 0.

The present invention particularly provides the aromatic compounds selected from the group consisting of:

  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methoxyphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-fluorophenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methylphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzenesulfonamide,
  • N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperazin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-{6-[(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenyl)methylamino]pyridin-3-yl}-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-{6-[4-(4-benzylpiperazine-1-carbonyl)-phenoxy]pyridin-3-yl}-4-trifluoromethylbenzamide,
  • N-{6-[4-(4-benzylpiperazine-1-carbonyl)phenoxy]pyridin-3-yl}-3,4-dichlorobenzamide,
  • N-[6-({4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenyl}methylamino)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-fluorophenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methoxyphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}phenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • 1-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-3-(3,4-dichlorophenyl)-1-ethylurea,
  • N-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-(6-{4-[3-(4-piperonylpiperazine-1-carbonyl)piperidin-1-yl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzamide,
  • N-[6-(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-{6-[(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenyl)methylamino]pyridin-3-yl}-4-trifluoromethylbenzamide,
  • N-(6-{4-[(2-{4-[4-(4-fluorobenzoyl)phenyl]-piperazin-1-yl}-2-oxoethyl)methylamino]-2-methoxy-phenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide,
  • 2-(4-piperonylpiperazin-1-yl)-N-{3-methyl-4-[5-(4-trifluoromethylphenoxymethyl)pyridin-2-yloxy]phenyl}-2-oxoacetamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-2-fluoro-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, and
  • 4-(3-{3-methyl-4-[5-(4-trifluoromethyl-benzoylamino)pyridin-2-yloxy]phenyl}-2-oxohexahydropyrimidin-1-yl)benzoic acid ethyl ester, or salts thereof.

The present invention provides processes for preparing the aromatic compound represented by the general formula (1) or a salt thereof according to any one of the processes described in Reaction formulas-1 to 46, 48, 49, 52, 59, 104, 105, 108 to 132 and 135 mentioned below.

The present invention provides a pharmaceutical composition for the treatment of fibrosis, which comprises an aromatic compound represented by the general formula (1A) or a salt thereof:


[wherein X1 represents a nitrogen atom or a group CH═, R1 represents a group ZR6,
Z represents a group N(R8)B, a group BN(R8), a group B0O, a group


a group CO, a group CH(OH), a group


a group N═CH, a group


a lower alkenylene group, a group NHCOB1, a group NHCOB2(W)u-, a group B0OB19a, a group


a group


a group


a group S, a lower alkynylene group, a lower alkylene group, a group


or a group CONHB18a-,
wherein R8 represents a hydrogen atom, a lower alkyl group that may have a lower alkoxy group as a substituent, a lower alkanoyl group, a phenyl lower alkyl group, or a lower alkylsulfonyl group,
B represents a group CO or a lower alkylene group,
B0 represents a lower alkylene group,
each of R9a and R9b, which are identical or different, represents a hydrogen atom or a lower alkyl group
R10a represents a hydrogen atom or a lower alkyl group,
B22a represents a lower alkylene group or a lower alkenylene group,
e represents 0 or 1,
B1 represents a lower alkenylene group that may have a phenyl group as a substituent,
B2 represents a lower alkylene group that may be substituted by a group selected from the group consisting of a lower alkoxy group and a phenyl group,
W represents an oxygen atom, a group NH, or a sulfur atom,
u represents 0 or 1,
B18a represents a lower alkylene group,
B19a represents a lower alkylene group,
B20a represents a lower alkylene group,
B21a represents a lower alkylene group,
R8d represents a hydrogen atom or a lower alkyl group,
k represents 2 or 3,
c represents 0 or 1,
d′ represents 0 or 1,
R10b represents a hydrogen atom or a lower alkyl group,
R6 represents a 5- to 15-membered monocyclic, dicyclic, or tricyclic saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (wherein, the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of an oxo group; an optionally halogenated lower alkoxy group; an optionally halogenated lower alkyl group; a halogen atom; a lower alkylsulfonyl group; a phenyl group that may be substituted, on the phenyl ring, by an optionally halogenated lower alkyl group; a lower alkylthio group; a pyrrolyl group; a benzoyl group; a lower alkanoyl group; a lower alkoxycarbonyl group; and an amino group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent), an adamantyl group, a naphthyl group (wherein, the naphthalene ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkyl group, a halogen atom, and an amino group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent), an alkyl group that may have a lower alkoxy group as a substituent, a cycloalkyl group that may be substituted, on the cycloalkyl ring, by a group selected from the group consisting of an amino-substituted lower alkyl group that may have a lower alkyl group on the amino group and a lower alkyl group that may have a halogen atom as a substituent, a lower alkenyl group that may have a halogen atom as a substituent, a lower alkanoyl group, a benzoyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group that may have a halogen atom as a substituent and a halogen atom, a group


a halogen atom-substituted lower alkyl group, or a cycloalkyl lower alkyl group,
R7 represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group that may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group that may have, as a substituent, a group selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group, and a cycloalkyl group, a cyano group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkylsulfonyl group, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a 5- or 6-membered saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (wherein the heterocyclic ring may be substituted, by an oxo group), or a lower alkoxycarbonyl lower alkyl group,
m represents an integer between 1 and 5, wherein when m represents 2 to 5, two to five R7s may be identical or different,
R2 represents a hydrogen atom, a halogen atom, or a lower alkyl group,
Y represents a group O, a group N(R5), a group CO, a group CH(OH), a lower alkylene group, a group S(O)n-, or a group C(═NOH),
R5 represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a benzoyl group, a phenyl lower alkyl group, or a cycloalkyl group,
n represents 0, 1, or 2,
A represents a group


or a group


p represents 1 or 2,
R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a group CONR11R12, or a cyano group,
wherein each of R11 and R12, which are identical or different, represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group, or R11 and R12, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring,
R4 represents an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group that may have an oxo group as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group that may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a group


a group


or a group -(T)l-N(R14)R15,
R13 represents a hydrogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a benzoyl group, a morpholino-substituted lower alkanoyl group, a piperazinyl carbonyl lower alkyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, a piperazinyl lower alkanoyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, a morpholinocarbonyl-substituted lower alkyl group, or an imidazolyl lower alkanoyl group,
R13a represents a hydrogen atom or a hydroxyl group,
T represents a lower alkylene group, a group N(R17)B3CO, a group (B19)eN(R8)CO, a group B4CO, a group -Q-B5CO, a group B6N(R19)B7CO, a group COB8, a group CH(OH)B9, a group COB10CO, a group CH(OH)B11CO, a group CO, a group SO2, or a group B23aCOCO,
wherein R17 represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkenyl group, an amino-substituted lower alkanoyl group that may have a lower alkyl group as a substituent, or a lower alkylsulfonyl group,
B3 represents a lower alkylene group,
B19 represents a lower alkylene group,
e represents 0 or 1,
R18 represents a hydrogen atom or a lower alkyl group,
B4 represents a lower alkenylene group or a lower alkylene group that may have a hydroxyl group as a substituent,
Q represents an oxygen atom or a group S(O)n- (wherein n has the same meanings as described above),
B5 represents a lower alkylene group,
B6 represents a lower alkylene group,
R19 represents a hydrogen atom or a lower alkanoyl group,
B7 represents a lower alkylene group,
B8 represents a lower alkylene group,
B9 represents a lower alkylene group,
B10 represents a lower alkylene group,
B11 represents a lower alkylene group,
B23a represents a lower alkylene group,
l represents 0 or 1,
each of R14 and R15, which are identical or different represents (1) a hydrogen atom, (2) an alkyl group that may have a hydroxyl group as a substituent, (3) a cycloalkyl group that may have a group selected from the group consisting of a hydroxyl group and a lower alkyl group as a substituent, (4) a phenoxy lower alkyl group, (5) a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group that may have a halogen atom as a substituent; a halogen atom; an amino lower alkoxy group that may have a lower alkyl group as a substituent; a hydroxyl group-substituted lower alkyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group that may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group that may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group that may have a lower alkyl group as a substituent on the piperazine ring; a pyrrolidinyl group that may have an oxo group as a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group, (6) a phenoxy group, (7) a phenyl lower alkyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group that may have a halogen atom as a substituent, and a lower alkyl group, (8) a phenyl lower alkyl group that has a lower alkylenedioxy group as a substituent on the phenyl ring, (9) a lower alkanoyl group, (10) a lower alkoxycarbonyl-substituted lower alkyl group, (11) a carboxy-substituted lower alkyl group, (12) an amino group that may have a lower alkanoyl group as a substituent, (13) a 1,2,3,4-tetrahydroquinolyl group that may have 1 to 3 groups selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group as a substituent(s) on the tetrahydroquinoline ring, (14) a cycloalkyl lower alkyl group, (15) a piperazinyl lower alkanoyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (16) a pyridyl lower alkyl group, (17) an amino group-substituted lower alkyl group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, (18) a lower alkoxy lower alkyl group, (19) an imidazolyl group, (20) an imidazolyl lower alkyl group, (21) a 1,2,3,4-tetrahydroisoquinolylcarbonyl-substituted lower alkyl group, (22) a piperidinylcarbonyl group that may have a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, and a furyl lower alkyl group as a substituent on the piperidine ring, (23) a thiazolidinyl lower alkanoyl group that may have an oxo group as a substituent on the thiazolidine ring, (24) a piperidinyl group that may be substituted, on the piperidine ring, by a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group, and a furyl lower alkyl group, (25) a carbonyl lower alkyl group substituted by a group


(26) a carbonyl lower alkyl group substituted by a group


(27) a group COB20N(R36)R37, (26a) a pyrrolidinyl lower alkyl group, (27a) a morpholino lower alkyl group, (28a) a phenyl lower alkenyl group, (29a) an anilinocarbonyl lower alkyl group that may have a lower alkyl group as a substituent on the phenyl ring, (30a) an indolyl group, (31a) a piperazinyl lower alkyl group that may have, as a substituent on the piperazine ring, a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (32a) an amidino lower alkyl group that may have a lower alkyl group as a substituent, (33a) a fluorenyl group, (34a) a carbazolyl group that may have a lower alkyl group as a substituent on the carbazole ring, (35a) an amidino group that may have a lower alkyl group as a substituent, (36a) a piperazinyl-substituted oxalyl group that may have 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group as a substituent(s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent(s) on the piperazine ring, or (37a) a cyano-substituted lower alkyl group,
R34 represents an oxo group or a phenyl group,
d represents an integer between 0 and 3,
B20 represents a lower alkylene group,
R36 and R37, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein the heterocyclic group may be substituted by 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
R14 and R15, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated or unsaturated heterocyclic ring; or a group


wherein the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of (28) a phenyl-substituted lower alkyl group, which has 1 to 2 phenyl groups and which may have a pyridyl group on the lower alkyl group, wherein the phenyl ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkanoyl group, an amino group that may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group, (29) a carbamoyl group, (30) a pyridyl lower alkyl group that may have, as a substituent(s) on the pyridine ring, 1 to 3 groups selected from the group consisting of a hydroxyl group and a lower alkyl group that may have a hydroxyl group as a substituent, (31) a pyrrolyl lower alkyl group that may have 1 to 3 lower alkyl groups as a substituent(s) on the pyrrole ring, (32) a benzoxazolyl lower alkyl group, (33) a benzothiazolyl lower alkyl group, (34) a furyl lower alkyl group, (35) a benzoyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, an amino group that may have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group that may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group, (36) a pyrimidinyl group, (37) a pyrazinyl group, (38) a pyridyl group, (39) a lower alkoxycarbonyl group, (40) a thiazolidinyl lower alkanoyl group that may be substituted, on the thiazolidine ring, by a group selected from the group consisting of an oxo group and a group


(wherein each of Ra and Rb represents a lower alkyl group), (41) a lower alkyl group that may have a group selected from the group consisting of a hydroxyl group and a halogen atom as a substituent, (42) a lower alkanoyl group that may have a halogen atom as a substituent, (43) a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a carbamoyl group that may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a benzoyl group that may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group that may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group, (44) a phenyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (45) a naphthyl lower alkyl group, (46) a phenoxy group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group that may have a halogen atom as a substituent, and a lower alkoxy group that may have a halogen atom as a substituent, (47) a phenoxy lower alkyl group, (48) a phenyl lower alkoxy group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, and a lower alkoxy group that may have a halogen atom as a substituent, (49) a group (B12CO)t-N(R20)R21, (50) a group (CO)o-B13N(R22)R23, (51) a 1,2,3,4-tetrahydronaphthyl-substituted lower alkyl group that may be substituted, on the 1,2,3,4-tetrahydronaphthalene ring, by 1 to 5 lower alkyl groups as a substituent(s), (52) a cycloalkyl group that may have a hydroxyl group as a substituent, (53) a piperidinyl group that may be substituted, on the piperidine ring, by 1 to 3 lower alkyl groups as a substituent(s), (54) a quinolyl lower alkyl group, (55) a 1,2,3,4-tetrazolyl lower alkyl group that may have a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent on the tetrazole ring, (56) a thiazolyl lower alkyl group that may have a phenyl group as a substituent on the thiazole ring, (57) a benzoyl lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkoxy group and a halogen atom as a substituent(s) on the phenyl ring, (58) a piperidinyl lower alkyl group that may have a lower alkyl group as a substituent on the piperidine ring, (59) an imidazolyl group that may have 1 to 3 phenyl groups as a substituent(s) on the imidazole ring, (60) a benzimidazolyl group that may have 1 to 3 lower alkyl groups as a substituent(s) on the benzimidazole ring, (61) a pyridyl lower alkoxy group, (62) a 1,2,3,4-tetrahydroquinolyl lower alkyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring, (63) a 1,3,4-oxadiazolyl lower alkyl group that may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, (64) a cycloalkyl lower alkyl group, (65) a tetrahydropyranyl group, (66) a thienyl lower alkyl group, (67) a pyrimidinylcarbonyl group that may have an oxo group as a substituent on the pyrimidine ring, (68) a hydroxyl group, (69) a carboxy group, (70) a lower alkoxy lower alkyl group, (71) a lower alkoxy lower alkoxy group, (72) a benzoyloxy group, (73) a lower alkoxycarbonyl lower alkoxy group, (74) a carboxy lower alkoxy group, (75) a phenoxy lower alkanoyl group, (76) a 1,2,3,4-tetrahydroquinolylcarbonyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring, (77) a phenylsulfonyl group, (78) an imidazolyl lower alkanoyl group, (79) an imidazolyl lower alkyl group, (80) a pyridylcarbonyl group, (81) an imidazolylcarbonyl group, (82) a lower alkoxycarbonyl lower alkyl group, (83) a carboxy lower alkyl group, (84) a group (OB15)s-CON(R26)R27, (85) a group N(R28)COB16N(R29)R30, (86) a group N(R31)B7CON(R32)R33, (87) a benzoxazolyl group, (88a) a benzothienyl group, (89a) an oxo group, and (90a) a 1,2,3,4-tetrahydroquinolyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring,
B12 represents a lower alkylene group,
t represents 0 or 1,
each of R20 and R21, which are identical or different, represents a hydrogen atom; a cycloalkyl group; an amino group that may have a lower alkoxycarbonyl group as a substituent; a benzoyl group that may have 1 to 3 lower alkoxy groups as a substituent(s) on the phenyl ring; a lower alkyl group; a lower alkyl group having 1 to 2 phenyl groups that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, and a lower alkylthio group; a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxy group that may have a halogen atom as a substituent and a lower alkyl group that may have a halogen atom as a substituent; a lower alkoxycarbonyl group; a cycloalkyl lower alkyl group; a pyrrolidinyl lower alkyl group that may have 1 to 3 lower alkyl groups that may have a hydroxyl group as a substituent on the pyrrolidine ring; an amino-substituted lower alkyl group that may have a group selected from the group consisting of a phenyl group and a lower alkyl group as a substituent; a 1,2,3,4-tetrahydronaphthyl-substituted lower alkyl group that may have 1 to 5 lower alkyl groups as a substituent(s) on the 1,2,3,4-tetrahydronaphthalene ring; a naphthyl lower alkyl group; a pyridyl lower alkyl group; a quinolyl lower alkyl group; a 1,2,3,4-tetrazolyl lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent(s) on the tetrazole ring; a 1,2,4-triazolyl lower alkyl group; a tetrahydrofuryl lower alkyl group that may have a hydroxyl group as a substituent on the lower alkyl group; a phenoxy lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a nitro group as a substituent(s) on the phenyl ring; a phenyl lower alkanoyl group; a lower alkanoyl group that may have a halogen atom as a substituent; an imidazolyl lower alkanoyl group; a lower alkoxycarbonyl lower alkyl group; a pyridyl group; or a carboxy lower alkyl group, or R20 and R21, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring, wherein the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkyl group, a phenyl group that may have 1 to 3 groups selected from the group consisting of a halogen atom and a lower alkyl group that may have a halogen atom as a substituent(s) on the phenyl ring, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
o represents 0 or 1,
B13 represents a lower alkylene group,
each of R22 and R23, which are identical or different, represents a hydrogen atom, a lower alkyl group, a benzoyl group that may have 1 to 3 lower alkoxy groups as a substituent(s) on the phenyl ring, a phenoxy lower alkyl group that may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group, or a phenyl group, or R22 and R23, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring, wherein the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
B15 represents a lower alkylene group,
s represents 0 or 1,
each of R26 and R27, which are identical or different, represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or an imidazolyl lower alkyl group, or R26 and R27, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring, wherein the heterocyclic ring may be substituted by 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group as a substituent on the phenyl ring, as a substituent(s),
R28 represents a hydrogen atom or a lower alkyl group,
B16 represents a lower alkylene group,
R29 and R30, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
R31 represents a hydrogen atom or a lower alkyl group,
B17 represents a lower alkylene group,
R32 and R33, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein the heterocyclic ring may be substituted by 1 to 3 groups selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring].

Further, the present invention provides the pharmaceutical composition for the treatment of fibrosis, comprising the aromatic compound represented by the general formula (1) or a salt thereof mentioned above.

The present invention provides the above-mentioned pharmaceutical composition for the treatment of fibrosis, comprising the aromatic compound or a salt thereof mentioned above, wherein the aromatic compound is selected from the group consisting of

  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methoxyphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-fluorophenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methylphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzenesulfonamide,
  • N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperazin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-{6-[(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenyl)methylamino]pyridin-3-yl}-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-{6-[4-(4-benzylpiperazine-1-carbonyl)-phenoxy]pyridin-3-yl}-4-trifluoromethylbenzamide,
  • N-{6-[4-(4-benzylpiperazine-1-carbonyl)phenoxy]pyridin-3-yl}-3,4-dichlorobenzamide,
  • N-[6-({4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenyl}methylamino)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-fluorophenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methoxyphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}phenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • 1-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-3-(3,4-dichlorophenyl)-1-ethylurea,
  • N-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide,
  • N-[6-(4-{[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-3,4-dichlorobenzamide,
  • N-(6-{4-[3-(4-piperonylpiperazine-1-carbonyl)piperidin-1-yl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzamide,
  • N-[6-(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide,
  • N-{6-[(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenyl)methylamino]pyridin-3-yl}-4-trifluoromethylbenzamide,
  • N-(6-{4-[(2-{4-[4-(4-fluorobenzoyl)phenyl]-piperazin-1-yl}-2-oxoethyl)methylamino]-2-methoxyphenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide,
  • 2-(4-piperonylpiperazin-1-yl)-N-{3-methyl-4-[5-(4-trifluoromethylphenoxymethyl)pyridin-2-yloxy]phenyl}-2-oxoacetamide,
  • N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-2-fluoro-4-trifluoromethylbenzamide,
  • N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, and
  • 4-(3-{3-methyl-4-[5-(4-trifluoromethylbenzoylamino)pyridin-2-yloxy]phenyl}-2-oxohexahydropyrimidin-1-yl)benzoic acid ethyl ester, or salts thereof.

The present invention provides the above-mentioned pharmaceutical composition for the treatment of fibrosis, wherein the fibrosis is lung fibrosis. The present invention provides the above-mentioned pharmaceutical composition for the treatment of fibrosis, wherein the fibrosis is hepatic fibrosis. The present invention provides the above-mentioned pharmaceutical composition for the treatment of fibrosis, wherein the fibrosis is glomerulosclerosis.

Specific examples of each group represented by the general formula (1) are as follows.

Examples of the lower alkynylene group include linear or branched alkynylene groups having 2 to 6 carbon atoms which have 2 to 6 triple bonds such as ethynylene, 1-propynylene, 1-methyl-1-propynylene, 2-methyl-1-propynylene, 2-propynylene, 2-butynylene, 1-butynylene, 3-butynylene, 2-pentynylene, 1-pentynylene, 3-pentynylene, 4-pentynylene, 2-pentyn-4-ynylene, 2-hexynylene, 1-hexynylene, 5-hexynylene, 3-hexynylene, 4-hexynylene, 3,3-diethyl-1-propynylene, 2-ethyl-1-propynylene groups.

Examples of the amino group which may have a substituent selected from the group consisting of a lower alkyl group and a lower alkanoyl group include amino groups which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkanoyl group having 1 to 6 carbon atoms such as amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino, diacetylamino, N-acetyl-N-methylamino, N-acetyl-N-ethylamino groups.

Examples of the benzoyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group which may have a halogen atom as a substituent and a halogen atom) include benzoyl groups (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents and a halogen atom) such as benzoyl, 3,4-difluorobenzoyl, 2-fluorobenzoyl, 3-bromobenzoyl, 4-iodobenzoyl, 4-methylbenzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 2-ethylbenzoyl, 3-ethylbenzoyl, 4-ethylbenzoyl, 4-isopropylbenzoyl, 3-butylbenzoyl, 4-pentylbenzoyl, 4-hexylbenzoyl, 3,4-dimethylbenzoyl, 3,4-diethylbenzoyl, 2,4-dimethylbenzoyl, 2,5-dimethylbenzoyl, 2,6-dimethylbenzoyl, 3,4,5-trimethylbenzoyl, 2-trifluoromethylbenzoyl, 3-trifluoromethylbenzoyl, 4-trifluoromethylbenzoyl, 2-(bromomethyl)benzoyl, 3-(2-chloroethyl)benzoyl, 4-(2,3-dichloropropyl)benzoyl, 4-(4-fluorobutyl)benzoyl, 3-(5-chloropentyl)benzoyl, 4-(5-bromohexyl)benzoyl, 4-(5,6-dibromohexyl)benzoyl, 3,4-di(trifluoromethyl)benzoyl, 3,4-di(4,4,4-trichlorobutyl)benzoyl, 2,4-di(3-chloro-2-methylpropyl)benzoyl, 2,5-di(3-chloropropyl)benzoyl, 2,6-di(2,2,2-trifluoroethyl)benzoyl, 3,4,5-tri(trifluoromethyl)benzoyl, 4-(2,2,2-trichloroethyl)benzoyl, 2-methyl-4-trifluoromethylbenzoyl, 3-ethyl-4-trichloromethylbenzoyl, 2-chloro-4-trifluoromethylbenzoyl, 3-ethyl-4-fluorobenzoyl, 3-fluoro-4-trichloromethylbenzoyl, 2-methyl-3-trifluoromethyl-4-trifluoromethylbenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 2,3-dibromobenzoyl, 2,4-diiodobenzoyl, 2,5-difluorobenzoyl, 2,6-dichlorobenzoyl, 2,4,6-trichlorobenzoyl, 2,4-difluorobenzoyl, 3,5-difluorobenzoyl, 2,6-difluorobenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 2,5-dichlorobenzoyl, 3,4-dichlorobenzoyl, 2,6-dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,4,6-trifluorobenzoyl, 2,4-difluorobenzoyl groups.

Examples of the halogen substituted lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms which have 1 to 3 halogen atoms as substituents such as a trifluoromethyl group, trichloromethyl group, chloromethyl group, bromomethyl group, fluoromethyl group, iodomethyl group, difluoromethyl group, dibromomethyl group, dichloromethyl group, 2-chloroethyl group, 2,2,2-trifluoroethyl group, 2,2,2-trichloroethyl group, 3-chloropropyl group, 2,3-dichloropropyl group, 4,4,4-trichlorobutyl group, 4-fluorobutyl group, 5-chloropentyl group, 3-chloro-2-methylpropyl group, 5-bromohexyl group, and 5,6-dibromohexyl group.

Examples of the lower alkanoyl substituted amino group include linear or branched alkanoyl groups having 2 to 6 carbon atoms which have 1 to 3 halogen atoms as substituents such as a acetyl amino group, propionyl amino group, butyryl amino group, pentanoyl amino group, 2-methylpropionyl amino group and hexanoyl amino group.

Examples of the piperazinyl substituted oxalyl group which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a phenyl lower alkyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group) and a pyridyl lower alkyl group include piperazinyl substituted oxalyl groups which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a phenylalkyl group of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms (and which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkylenedioxy group having 1 to 4 carbon atoms and a linear or branched alkoxy group having 1 to 6 carbon atoms) and a pyridylalkyl group of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 4-(3,4-methylenedioxybenzyl)-(1-,2-, or 3-)piperazinyloxalyl, 4-(2-,3-, or 4-pyridylmethyl)-(1-, 2-, or 3-)piperazinyloxalyl, 4-(3,4-dimethoxybenzyl)-(1-, 2-, or 3-)piperazinyloxalyl, 4-(2,3-methylenedioxybenzyl)-(1-,2-, or 3-)piperazinyloxalyl, 4-(3,4-ethylenedioxybenzyl)-(1-,2-, or 3-)piperazinyloxalyl, 4-[2-(2-,3-, or 4-pyridyl)ethyl]-(1-, 2-, or 3-)piperazinyloxalyl, 4-[3-(2-,3-, or 4-pyridyl)propyl-(1-,2-, or 3-)piperazinyloxalyl, 2,4-bis(2-,3-, or 4-pyridylmethyl)-(1-,2-, or 3-)piperazinyloxalyl, 2-(3,4-methylenedioxybenzyl)-4-(2-,3-, or 4-pyridylmethyl)-(1-,2-, or 3-)piperazinyloxalyl, 2,3,4-tri(2-,3-, or 4-pyridylmethyl)-(1-,2-, or 3-)piperazinyloxalyl groups.

Examples of the cyano substituted lower alkyl group include cyanoalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a cyanomethyl group, 2-cyanoethyl group, 1-cyanoethyl group, 3-cyanopropyl group, 4-cyanobutyl group, 5-cyanopentyl group, 6-cyanohexyl group, 1,1-dimethyl-2-cyanoethyl group, and 2-methyl-3-cyanopropyl group.

Examples of the carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group include carbamoyl groups which may have 1 or 2 groups selected from the group consisting of a linear or branched alkyl group having 1 to 0.6 carbon atoms which has a linear or branched alkoxy group having 1 to 6 carbon atoms and a linear or branched alkyl group having 1 to 6 carbon atoms such as carbamoyl, N-(2-methoxyethyl)carbamoyl, methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, tert-butylcarbamoyl, pentylcarbamoyl, hexylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl, dipropylcarbamoyl, dibutylcarbamoyl, dipentylcarbamoyl, dihexylcarbamoyl, N-methyl-N-ethylcarbamoyl, N-ethyl-N-propylcarbamoyl, N-methyl-N-butylcarbamoyl, N-methyl-N-hexylcarbamoyl, N-(methoxymethyl)carbamoyl, N-(3-propoxypropyl)carbamoyl, N-(4-butoxybutyl)carbamoyl, N-(4-ethoxybutyl)carbamoyl, N-(5-pentyloxypentyl)carbamoyl, N-(5-methoxypentyl)carbamoyl, N-(6-hexyloxyhexyl)carbamoyl, di(2-methoxyethyl)carbamoyl, N-(2-methoxyethyl)-N-methylcarbamoyl, N-(2-methoxyethyl)-N-ethylcarbamoyl groups.

Examples of the phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group which may have a halogen atom include phenyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a halogen atom and a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms such as phenyl, 3,4-difluorophenyl, 2-fluorophenyl, 3-bromophenyl, 4-iodophenyl, 4-methylphenyl, 2-methylphenyl, 3-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, 3-ethyl-4-trichloromethylphenyl, 2-chloro-4-trifluoromethylphenyl, 3-ethyl-4-fluorophenyl, 3-fluoro-4-trichloromethylphenyl, 2-methyl-3-trifluoromethyl-4-trifluoromethylphenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 2,3-dibromophenyl, 2,4-diiodophenyl, 2,5-difluorophenyl, 2,6-dichlorophenyl, 2,4,6-trichlorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,4,6-trifluorophenyl, 2,4-difluorophenyl groups.

Examples of the lower alkenylene group include linear or branched alkenylene groups having 2 to 6 carbon atoms which have 1 to 3 double bonds such as vinylene, 1-propenylene, 1-methyl-1-propenylene, 2-methyl-1-propenylene, 2-propenylene, 2-butenylene, 1-butenylene, 3-butenylene, 3-pentenylene, 1-pentenylene, 2-pentenylene, 4-pentenylene, 1,3-butadienylene, 1,3-pentadienylene, 2-penten-4-ynylene, 2-hexenylene, 1-hexenylene, 5-hexenylene, 3-hexenylene, 4-hexenylene, 3,3-dimethyl-1-propenylene, 2-ethyl-1-propenylene, 1,3,5-hexatrienylene, 1,3-hexadienylene, and 1,4-hexadienylene.

Examples of the lower alkoxy group include linear or branched alkoxy groups having 1 to 6 carbon atoms such as a methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, tert-butoxyl group, pentyloxy group, and hexyloxy group.

Examples of the lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms such as a methyl group, ethyl group, propyl group, isopropyl group, 2,2-dimethylpropyl group, 1-ethylpropyl group, butyl group, isobutyl group, tert-butyl group, isopentyl group, pentyl group, and hexyl group.

Examples of the lower alkyl group which may have a lower alkoxy group as a substituent include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 6 carbon atoms which may have a linear or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as a methoxymethyl group, 1-ethoxyethyl group, 2-methoxyethyl group, 2-propoxyethyl group, 3-isopropoxypropyl group, 4-butoxybutyl group, 5-pentyloxypentyl group, 6-hexyloxyhexyl, 1,1-dimethyl-2-methoxyethyl group, 2-methyl-3-ethoxypropyl, and 3-methoxypropyl group.

Examples of the lower alkanoyl group include alkanoyl groups having 1 to 6 carbon atoms such as a formyl group, acetyl group, propionyl group, butyryl group, isobutyryl group, pentanoyl group, tert-butylcarbonyl, and hexanoyl group.

Examples of the phenyl lower alkyl group include phenylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a benzyl group, 2-phenylethyl group, 1-phenylethyl group, 3-phenylpropyl group, 4-phenylbutyl group, 5-phenylpentyl group, 6-phenylhexyl group, 1,1-dimethyl-2-phenylethyl group, and 2-methyl-3-phenylpropyl group.

Examples of the phenyl lower alkyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group), include, in addition to the above described phenyl lower alkyl groups, phenylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms (and which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkylenedioxy group having 1 to 4 carbon atoms and a linear or branched alkoxy group having 1 to 6 carbon atoms) such as 3,4-methylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2-(2,3-ethylenedioxyphenyl)ethyl, 1-(3,4-trimethylenedioxyphenyl)ethyl, 3-(2,3-tetramethylenedioxyphenyl)propyl, 4-(3,4-methylenedioxyphenyl)butyl, 5-(2,3-ethylenedioxyphenyl)pentyl, 6-(3,4-trimethylenedioxyphenyl)hexyl, 1,1-dimethyl-2-(2,3-methylenedioxyphenyl)ethyl, 2-methyl-3-(3,4-ethylenedioxyphenyl)propyl, 2-methoxybenzyl, 2-(2-methoxyphenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 4-methoxybenzyl, 1-(2-ethoxyphenyl)ethyl, 3-(3-ethoxyphenyl)propyl, 4-(4-ethoxyphenyl)butyl, 5-(4-isopropoxyphenyl)pentyl, 6-(3-butoxyphenyl)hexyl, 1,1-dimethyl-2-(4-pentyloxyphenyl)ethyl, 2-methyl-3-(4-hexyloxyphenyl)propyl, 3,4-dimethoxybenzyl, 3,4-diethoxybenzyl, 2,4-dimethoxybenzyl, 2,5-dimethoxybenzyl, 2,6-dimethoxybenzyl, 3,4,5-trimethoxybenzyl groups.

Examples of the lower alkylene group include linear or branched alkylene groups having 1 to 6 carbon atoms such as a methylene group, ethylene group, trimethylene group, 2-methyltrimethylene group, 2,2-dimethylethylene group, 2,2-dimethyltrimethylene group, 1-methyltrimethylene group, methylmethylene group, ethylmethylene group, tetramethylene group, pentamethylene group, and hexamethylene group.

Examples of the lower alkenylene group which may have a phenyl group as a substituent include linear or branched alkenylene groups having 2 to 6 carbon atoms which have 1 to 3 double bonds and may have a phenyl group as a substituent such as vinylene, 1-propenylene, 1-methyl-1-propenylene, 2-methyl-1-propenylene, 2-propenylene, 2-butenylene, 1-butenylene, 3-butenylene, 2-pentenylene, 1-pentenylene, 3-pentenylene, 4-pentenylene, 1,3-butadienylene, 1,3-pentadienylene, 2-penten-4-ynylene, 2-hexenylene, 1-hexenylene, 5-hexenylene, 3-hexenylene, 4-hexenylene, 3,3-dimethyl-1-propenylene, 2-ethyl-1-propenylene, 1,3,5-hexatrienylene, 1,3-hexadienylene, 1,4-hexadienylene, 1-phenylvinylene, 3-phenyl-1-propenylene, 3-phenyl-1-methyl-1-propenylene, 3-phenyl-2-methyl-1-propenylene, 1-phenyl-2-propenylene, 1-phenyl-2-butenylene, 3-phenyl-1-butenylene, 1-phenyl-3-butenylene, 5-phenyl-2-pentenylene, 4-phenyl-1-pentenylene, 2-phenyl-3-pentenylene, 1-phenyl-4-pentenylene, 1-phenyl-1,3-butadienylene, 1-phenyl-1,3-pentadienylene, 1-phenyl-2-penten-4-ynylene, 1-phenyl-2-hexenylene, 3-phenyl-1-hexenylene, 4-phenyl-5-hexenylene, 6-phenyl-3-hexenylene, 5-phenyl-4-hexenylene, 1-phenyl-3,3-dimethyl-1-propenylene, 1-phenyl-2-ethyl-1-propenylene, 6-phenyl-1,3,5-hexatrienylene, 1-phenyl-1,3-hexadienylene, 2-phenyl-1,4-hexadienylene groups.

Examples of the lower alkylene group which may be substituted with a group selected from the group consisting of a lower alkoxy group and a phenyl group include, in addition to the above described lower alkylene groups, linear or branched alkylene groups having 1 to 6 carbon atoms which may be substituted with 1 or 2 groups selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms and a phenyl group such as methoxymethylene, 2-phenylethylene, 3-ethoxytrimethylene, 1-propoxy-2-methyltrimethylene, 1-phenyl-2,2-dimethylethylene, 3-phenyl-2,2-dimethyltrimethylene, 2-butoxy-1-methyltrimethylene, phenylmethylmethylene, 2-pentyloxyethylmethylene, 4-phenyl-2-hexyloxytetramethylene, 3-phenylpentamethylene, 5-phenylhexamethylene, ethoxymethylene, 1-phenylethylene, 3-phenyltrimethylene, 2-phenyl-1-methoxyethylene groups.

Examples of the 5- to 15-membered monocyclic, bicyclic or tricyclic saturated or unsaturated heterocyclic group which has 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridyl, 1,2,5,6-tetrahydropyridyl, 1,2,4-triazolyl, 1,2,3-triazolyl, 1,2,5-triazolyl, thiazolidinyl, 1,2,3,4-tetrazolyl, thienyl, quinolyl, 1,4-dihydroquinolyl, benzothiazolyl, pyrazyl, pyrimidyl, pyridazyl, 2H-pyrrolyl, pyrrolyl, 1,3,4-oxadiazolyl, tetrahydropyranyl, tetrahydrofuryl, furazanyl, carbostyryl, 3,4-dihydrocarbostyryl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, indolyl, isoindolyl, indolinyl, benzoimidazolyl, benzoxazolyl, imidazolidinyl, isoquinolyl, quinazolidinyl, quinoxalinyl, cinnolinyl, phthalazinyl, carbazoyl, acridinyl, chromanyl, isoindolinyl, isochromanyl, pyrazolyl, imidazolyl, pyrazolidinyl, phenothiazinyl, benzofuryl, 2,3-dihydrobenzo[b]furyl, benzothienyl, phenoxatiynyl, phenoxadinyl, 4H-chromenyl, 1H-indazolyl, phenazinyl, xanthenyl, thianthrenyl, 2-imidazolinyl, 2-pyrrolinyl, furyl, oxazolyl, isoxazolyl, isoxazolidinyl, thiazolyl, isothiazolyl, pyranyl, 2-thiazolinyl, 2-pyrazolinyl, quinuclidinyl, 1,4-benzoxadinyl, 3,4,-dihydro-2H-1,4-benzoxadinyl, 3,4-dihydro-2H-1,4-benthiazinyl, 1,4-benzothiazinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,3-dithia-2,4-dihydronaphthalenyl, phenanthridinyl, 1,4-dithianaphthalenyl, dibenz[b,e]azepine, 6,11-dihydro-5H-dibenz[b,e]azepine groups.

Examples of the halogen atom include a fluorine atom, chlorine atom, bromine atom and iodine atom.

Examples of the lower alkoxy group which may have a halogen atom as a substituent include linear or branched alkoxy groups having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxy, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy, 5-chloropentyloxy, 3-chloro-2-methylpropoxy, 6-bromohexyloxy, 5,6-dichlorohexyloxy groups.

Examples of the lower alkyl group which may have a halogen atom as a substituent include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as a trifluoromethyl group, trichloromethyl group, chloromethyl group, dichloromethyl group, bromomethyl group, fluoromethyl group, iodomethyl group, difluoromethyl group, dibromomethyl group, dichloromethyl group, 2-chloroethyl group, 2,2,2-trifluoroethyl group, 2,2,2-trichloroethyl group, 3-chloropropyl group, 2,3-dichloropropyl group, 4,4,4-trichlorobutyl group, 4-fluorobutyl group, 5-chloropentyl group, 3-chloro-2-methylpropyl group, 5-bromohexyl group, and 5,6-dibromohexyl group.

Examples of the lower alkylsulfonyl group include linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms such as a methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, isopropylsulfonyl group, butylsulfonyl group, tert-butylsulfonyl group, pentylsulfonyl group, and hexylsulfonyl group.

Examples of the phenyl group which may be substituted on the phenyl ring with a lower alkyl group which may have a halogen atom include phenyl groups which may be substituted with 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, 3-ethyl-4-trichloromethyl groups.

Examples of the lower alkylthio group include linear or branched alkylthio groups having 1 to 6 carbon atoms such as a methylthio group, ethylthio group, propylthio group, isopropylthio group, butylthio group, tert-butylthio group, pentylthio group, and hexylthio group.

Examples of the naphthyl group which may be substituted on the naphthalene ring with 1 to 3 substituents selected from the group consisting of a lower alkyl group, a halogen atom, and an amino group which may have a substituent selected from the group consisting of a lower alkyl group and a lower alkanoyl group include naphthyl groups which may have, on the naphthalene ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms, a halogen atom, and an amino group which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkanoyl group having 1 to 6 carbon atoms such as (1- or 2-)naphthyl, 1-methyl-(2-,3-,4-,5-,6-,7-, or 8-)naphthyl, 2-ethyl-(1-,3-,4-,5-,6-,7-, or 8-)naphthyl, 3-n-propyl-(1-,2-,4-,5-,6-,7-, or 8-)naphthyl, 4-n-butyl-(1-,2-,3-,5-,6-,7-, or 8-)naphthyl, 4-methyl-(1-,2-,3-,5-,6-,7-, or 8-)naphthyl, 5-n-pentyl-(1-,2-,3-,4-,6-,7-, or 8-)naphthyl, 6-n-hexyl-(1-,2-,3-,4-,5-,7-, or 8-)naphthyl, 1,7-dimethyl-(2-,3-,4-,5-,6-, or 8-)naphthyl, 1,2,8-trimethyl-(3-,4-,5-,6-, or 7-)naphthyl, 1-dimethylamino-(2-,3-,4-,5-,6-,7-, or 8-)naphthyl, 2-dimethylamino-(1-,3-,4-,5-,6-,7-, or 8-)naphthyl, 3-methylamino-(1-,2-,4-,5-,6-,7-, or 8-)naphthyl, 5-amino-(1-,2-,3-,4-,6-,7-, or 8-)naphthyl, 5-dimethylamino-(1-,2-,3-,4-,6-,7-, or 8-)naphthyl, 4-(N-methyl-N-ethylamino)-(1-,2-, 3-,5-,6-,7-, or 8-)naphthyl, 1-methyl-2-dimethylamino-(3-,4-,5-,6-,7-, or 8-)naphthyl, 1-chloro-(2-,3-,4-,5-,6-,7-, or 8-)naphthyl, 1-acetylamino-(2-,3-,4-,5-,6-,7-, or 8-)naphthyl groups.

Examples of the alkyl group which may have a lower alkoxy group as a substituent include, in addition to the above described alkyl groups which may have a lower alkoxy group as a substituent, linear or branched alkyl groups having 1 to 8 carbon atoms which may have a linear or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as a heptyl group, 1-ethylpentyl group, octyl group, 7-methoxyheptyl group, 1-ethoxyheptyl group, 2-propoxyl-1-ethylpentyl group, 3-isopropoxyoctyl group, 7-butoxyheptyl group, 8-pentyloxyoctyl group, and 5-hexyloxy-1-ethylpentyl group.

Examples of the amino substituted lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms such as aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diethylaminoethyl, 2-diisopropylaminoethyl, (N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl groups.

Examples of the cycloalkyl group include cycloalkyl groups having 3 to 16 carbon atoms such as a cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclononyl group, cyclodecyl group, cycloundecyl group, cyclododecyl group, cyclotridecyl group, cycloteradecyl group, cyclopentadecyl group, and cyclohexadecyl group.

Examples of the cycloalkyl group which may be substituted with a group selected from the group consisting of an amino substituted lower alkyl group which may have a lower alkyl group and a lower alkyl group which may have a halogen as a substituent include cycloalkyl groups having 3 to 16 carbon atoms which may be substituted on the cycloalkyl ring with 1 to 3 groups selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms and a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as 4-dimethylaminomethylcyclohexyl, 2-(aminomethyl)cyclopropyl, 3-(2-aminomethyl)cyclobutyl, 2-(1-aminoethyl)cyclopentyl, 3-(3-aminopropyl)cyclohexyl, 3-(4-aminobutyl)cycloheptyl, 4-(5-aminopentyl)cyclooctyl, 4-(6-aminohexyl)cyclohexyl, 2-(1,1-dimethyl-2-aminoethyl)cycloheptyl, 3-(2-methyl-3-aminopropyl)cyclopentyl, 3-(methylaminomethyl)cyclohexyl, 2-(1-ethylaminoethyl)cyclooctyl, 2-(2-propylaminoethyl)cyclohexyl, 3-(3-isopropylaminopropyl)cyclopentyl, 4-(4-butylaminobutyl)cycloheptyl, 2-(5-pentylaminopentyl)cyclohexyl, 2-(6-hexylaminohexyl)cyclopentyl, 3-(dimethylaminomethyl)cyclohexyl, 3-[(N-ethyl-N-propylamino)methyl]cycloheptyl, 4-[2-(N-methyl-N-hexylamino)ethyl]cyclooctyl, 4-dimethylaminomethylcyclononyl, 2-(aminomethyl)cyclodecyl, 3-(2-aminomethyl)cycloundecyl, 2-(1-aminoethyl)cyclododecyl, 3-(3-aminopropyl)cyclotridecyl, 3-(4-aminobutyl)cyclotetradecyl, 4-(5-aminopentyl)cyclopentadecyl, 4-(6-aminohexyl)cyclohexadecyl, 2-(1,1-dimethyl-2-aminoethyl)cyclononyl, 3-(2-methyl-3-aminopropyl)cyclodecyl, 3-(methylaminomethyl)cycloundecyl, 2-(1-ethylaminoethyl)cyclododecyl, 2-(2-propylaminoethyl)cyclotridecyl, 3-(3-isopropylaminopropyl)cyclotetradecyl, 4-(4-butylaminobutyl)cyclopentadecyl, 2-(5-pentylaminopentyl)cyclohexadecyl, 2-(6-hexylaminohexyl)cyclononyl, 3-(dimethylaminomethyl)cyclododecyl, 3-[(N-ethyl-N-propylamino)methyl]cyclodecyl, 4-[2-(N-methyl-N-hexylamino)ethyl]cyclohexadecyl, 2,2-dimethylcyclopropyl, 2-trifluoromethylcyclopropyl groups.

Examples of the lower alkenyl group include linear or branched alkenyl groups having 2 to 6 carbon atoms which have 1 to 3 double bonds such as a vinyl group, 1-propenyl group, 1-methyl-1-propenyl group, 2-methyl-1-propenyl group, 2-propenyl group, 2-butenyl group, 1-butenyl group, 3-butenyl group, 2-pentenyl group, 1-pentenyl group, 3-pentenyl group, 4-pentenyl group, 1,3-butadienyl group, 1,3-pentadienyl group, 2-penten-4-ynyl group, 2-hexenyl group, 1-hexenyl group, 5-hexenyl group, 3-hexenyl group, 4-hexenyl group, 3,3-dimethyl-1-propenyl group, 2-ethyl-1-propenyl group, 1,3,5-hexatrienyl group, 1,3-hexadienyl group, and 1,4-hexadienyl group.

Examples of the lower alkenyl group which may have a halogen atom as a substituent include, in addition to the above described lower alkenyl groups, linear or branched alkenyl groups having 2 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents and 1 to 3 double bonds such as 3,3,3-trifluoro-1-propenyl, 2-bromovinyl, 3-chloro-1-propenyl, 3-iodo-1-methyl-1-propenyl, 3-fluoro-2-methyl-1-propenyl, 2-butenyl, 4,4,3-trichloro-1-butenyl, 4,4-difluoro-3-butenyl, 5-fluoro-2-pentenyl, 5,5,3-tribromo-1-pentenyl, 5-chloro-3-pentenyl, 5,5,5-trifluoro-4-pentenyl, 4-chloro-1,3-butadienyl, 5-fluoro-1,3-pentadienyl, 5-bromo-2-penten-4-ynyl, 6-fluoro-2-hexenyl, 6,6,5-trifluoro-1-hexenyl, 6-chloro-5-hexenyl, 5-bromo-3-hexenyl, 6-chloro-4-hexenyl, 3,3-dimethyl-2-chloro-1-propenyl, 3-fluoro-2-ethyl-1-propenyl, 6-chloro-1,3,5-hexatrienyl, 6-bromo-1,3-hexadienyl, 6-fluoro-1,4-hexadienyl groups.

Examples of the lower alkylenedioxy group include linear or branched alkylene groups having 1 to 4 carbon atoms such as a methylenedioxy group, ethylenedioxy group, trimethylenedioxy group, and tetramethylenedioxy group.

Examples of the amino group which may have a substituent selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group and a cycloalkyl group include amino groups which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkanoyl group having 1 to 6 carbon atoms, a benzoyl group, and a cycloalkyl group having 3 to 16 carbon atoms such as amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-methyl-N-acetylamino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino, N-ethyl-N-acetylamino, N-benzoylamino, N-ethyl-N-benzoylamino, N-methyl-N-benzoylamino, N-acetyl-N-benzoylamino, cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, cycloheptylamino, cyclooctylamino, N-methyl-N-cyclohexylamino, N-methyl-N-cyclopentylamino, N-methyl-N-cycloheptylamino, N-cyclohexyl-N-acetylamino, N-cyclopentyl-N-benzoylamino, cyclononylamino, cyclodecylamino, cyclododecylamino, cyclotridecylamino, cyclotetradecylamino, cyclopentadecylamino, N-methyl-N-cyclohexadecylamino, N-methyl-N-cyclononylamino, N-methyl-N-cyclodecylamino, N-cycloundecyl-N-acetylamino, N-cyclohexadecyl-N-benzoylamino groups.

Examples of the lower alkanoyl group which may have a halogen atom as a substituent include, in addition to the above described lower alkanoyl groups, linear or branched alkanoyl groups having 2-6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as a 2,2,2-trifluoroacetyl group, 2,2,2-trichloroacetyl group, 2-chloroacetyl group, 2-bromoacetyl group, 2-fluoroacetyl group, 2-iodoacetyl group, 2,2-difluoroacetyl group, 2,2-dibromoacetyl group, 3,3,3-trifluoropropionyl group, 3,3,3-trichloropropionyl group, 3-chloropropionyl group, 2,3-dichloropropionyl group, 4,4,4-trichlorobutyryl group, 4-fluorobutyryl group, 5-chloropentanoyl group, 3-chloro-2-methylpropionyl group, 6-bromohexanoyl group, and 5,6-dibromohexanoyl group.

Examples of the lower alkoxycarbonyl group include linear or branched alkoxycarbonyl groups having 1 to 6 carbon atoms such as a methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, tert-butoxycarbonyl group, pentyloxycarbonyl group, and hexyloxycarbonyl group.

Examples of the lower alkanoyloxy group include linear or branched alkanoyloxy groups having 2 to 6 carbon atoms such as an acetyloxy group, propionyloxy group, butyryloxy group, isobutyryloxy group, pentanoyloxy group, tert-butylcarbonyloxy group, and hexanoyloxy group.

Examples of the 5- or 6-membered saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyridyl, 1,2,5,6-tetrahydropyridyl, thienyl, pyrazyl, pyrimidyl, pyridazyl, pyrrolyl, 2H-pyrrolyl, imidazolidinyl, pyrazolyl, imidazolyl, pyrazolidinyl, furazanyl, 2-imidazolinyl, imidazolidinyl, 2-pyrrolinyl, furyl, oxazolyl, isoxazolidinyl, isoxazolyl, thiazolyl, isothiazolyl, pyranyl, 2-pyrazolidinyl, 1,2,4-triazolyl, 1,2,3-triazolyl, 1,2,5-triazolyl, thiazolidinyl, 2-thiazolinyl, 1,2,3,4-tetrazolyl, 1,3,4-oxadiazolyl, tetrahydropyranyl, tetrahydrofuryl groups.

Examples of the 5- to 7-membered saturated heterocyclic ring formed by binding R11 and R12 each other, together with nitrogen atoms bound to them, through or not through a nitrogen atom, a sulfur atom or an oxygen atom, include a pyrrolidinyl group, piperidinyl group, piperazinyl group, morpholino group, thiomorpholino group, and homopiperazinyl group.

Examples of the imidazolyl lower alkyl group include imidazolylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a (1,2,4 or 5-)imidazolylmethyl group, 2-[(1,2,4 or 5-)imidazolyl]ethyl group, 1-[(1,2,4 or 5-)imidazolyl]ethyl group, 3-[(1,2,4 or 5-)imidazolyl]propyl group, 4-[(1,2,4 or 5-)imidazolyl]butyl group, 5-[(1,2,4 or 5-)imidazolyl]pentyl group, 6-[(1,2,4 or 5-)imidazolyl]hexyl group, 1,1-dimethyl-2-[(1,2,4 or 5-)imidazolyl]ethyl group, and 2-methyl-3-[(1,2,4 or 5-)imidazolyl]propyl group.

Examples of the 1,2,4-triazolyl lower alkyl group include 1,2,4-triazolylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1,3, or 5-)1,2,4-triazolylmethyl, 2-[(1,3, or 5-)1,2,4-triazolyl]ethyl, 1-[(1,3, or 5-)1,2,4-triazolyl]ethyl, 3-[(1,3, or 5-)1,2,4-triazolyl]propyl, 4-[(1,3, or 5-)1,2,4-triazolyl]butyl, 5-[(1,3, or 5-)1,2,4-triazolyl]pentyl, 6-[(1,3, or 5-)1,2,4-triazolyl]hexyl, 1,1-dimethyl-2-[(1,3, or 5-)1,2,4-triazolyl]ethyl, 2-methyl-3-[(1,3, or 5-)1,2,4-triazolyl]propyl groups.

Examples of the 1,2,3-triazolyl lower alkyl group include 1,2,3-triazolylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1,4, or 5-)1,2,3-triazolylmethyl, 2-[(1,4, or 5-)1,2,3-triazolyl]ethyl, 1-[(1,4, or 5-)1,2,3-triazolyl]ethyl, 3-[(1,4, or 5-)1,2,3-triazolyl]propyl, 4-[(1,4, or 5-)1,2,3-triazolyl]butyl, 5-[(1,4, or 5-)1,2,3-triazolyl]pentyl, 6-[(1,4, or 5-)1,2,3-triazolyl]hexyl, 1,1-dimethyl-2-[(1,4, or 5-)1,2,3-triazolyl]ethyl, 2-methyl-3-[(1,4, or 5-)1,2,3-triazolyl]propyl groups.

Examples of the 1,2,5-triazolyl lower alkyl group include 1,2,5-triazolylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1,3, or 4-)1,2,5-triazolylmethyl, 2-[(1,3, or 4-)1,2,5-triazolyl]ethyl, 1-[(1,3, or 4-)1,2,5-triazolyl]ethyl, 3-[(1,3, or 4-)1,2,5-triazolyl]propyl, 4-[(1,3, or 4-)1,2,5-triazolyl]butyl, 5-[(1,3, or 4-)1,2,5-triazolyl]pentyl, 6-[(1,3, or 4-)1,2,5-triazolyl]hexyl, 1,1-dimethyl-2-[(1,3, or 4-)1,2,5-triazolyl]ethyl, 2-methyl-3-[(1,3, or 4-)1,2,5-triazolyl]propyl groups.

Examples of the pyrazolyl lower alkyl group include pyrazolylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a (1,3,4 or 5-)pyrazolylmethyl group, 2-[(1,3,4 or 5-)1,2,5-pyrazolyl]ethyl group, 1-[(1,3,4 or 5-)pyrazolyl]ethyl group, 3-[(1,3,4 or 5-)pyrazolyl]propyl group, 4-[(1,3,4 or 5-)pyrazolyl]butyl group, 5-[(1,3,4 or 5-)pyrazolyl]pentyl group, 6-[(1,3,4 or 5-)pyrazolyl]hexyl group, 1,1-dimethyl-2-[(1,3,4 or 5-)pyrazolyl]ethyl group, and 2-methyl-3-[(1,3,4 or 5-)pyrazolyl]propyl group.

Examples of the pyrimidinyl lower alkyl group include pyrimidinylalkyl groups which may have 1 to 3 oxo groups as substituents on the pyrimidine ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2,4,5, or 6-)pyrimidinylmethyl, 2-[(2,4,5, or 6-)pyrimidinyl]ethyl, 1-[(2,4,5, or 6-)pyrimidinyl]ethyl, 3-[(2,4,5, or 6-)pyrimidinyl]propyl, 4-[(2,4,5, or 6-)pyrimidinyl]butyl, 5-[(2,4,5, or 6-)pyrimidinyl]pentyl, 6-[(2,4,5, or 6-)pyrimidinyl]hexyl, 1,1-dimethyl-2-[(2,4,5, or 6-)pyrimidinyl]ethyl, 2-methyl-3-[(2,4,5, or 6-)pyrimidinyl]propyl, [(1,3,4, or 5-)2,6-dioxopyrimidinyl]methyl, [(1,3,4,5, or 6-)2-oxopyrimidinyl]methyl, [(1,2,4, or 5-)6-oxopyrimidinyl]methyl, [(1,2,5, or 6-)4-oxopyrimidinyl]methyl, [(1,3,5, or 6-)2,4-dioxopyrimidinyl]methyl, 2-[(4 or 6-)2,5-dioxopyrimidinyl]ethyl, 1-[(1,3,4, or 5-)2,6-dioxopyrimidinyl]ethyl, 3-[(1,3, or 5-)2,4,6-trioxopyrimidinyl]propyl, 4-[(1,3,4, or 5-)2,6-dioxopyrimidinyl]butyl, 5-[(4 or 6-)2,5-dioxopyrimidinyl]pentyl, 6-[(1,3,5, or 6-)2,4-dioxopyrimidinyl]hexyl, 1,1-dimethyl-2-[(1,3,4, or 5-)2,6-dioxopyrimidinyl]ethyl, 2-methyl-3-[(1,3,4, or 5-)2,6-dioxopyrimidinyl]propyl groups.

Examples of the 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group include 3,5-dioxoisoxazolidin-4-ylidenealkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a 3,5-dioxoisoxazolidin-4-ylidenemethyl group, 3,5-dioxoisoxazolidin-4-ylideneethyl group, 3,5-dioxoisoxazolidin-4-ylidenepropyl group, 3,5-dioxoisoxazolidin-4-ylideneisopropyl group, 3,5-dioxoisoxazolidin-4-ylidenebutyl group, 3,5-dioxoisoxazolidin-4-ylidenepentyl group, and 3,5-dioxoisoxazolidin-4-ylidenehexyl group.

Examples of the 1,2,4-oxadiazolyl lower alkyl group which may have a lower alkyl group as a substituent on the 1,2,4-oxadiazol ring include 1,2,4-oxadiazolylalkyl groups which may have a linear or branched alkyl group having 1 to 6 carbon atoms as a substituent on the 1,2,4-oxadiazol ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (3 or 5-)1,2,4-oxadiazolylmethyl, 2-[(3 or 5-)1,2,4-oxadiazolyl]ethyl, 1-[(3 or 5-)1,2,4-oxadiazolyl]ethyl, 3-[(3 or 5-)1,2,4-oxadiazolyl]propyl, 4-[(3 or 5-)1,2,4-oxadiazolyl]butyl, 5-[(3 or 5-)1,2,4-oxadiazolyl]pentyl, 6-[(3 or 5-)1,2,4-oxadiazolyl]hexyl, 1,1-dimethyl-2-[(3 or 5-)1,2,4-oxadiazolyl]ethyl, 2-methyl-3-[(3 or 5-)1,2,4-oxadiazolyl]propyl, 5-methyl-3-(1,2,4-oxadiazolyl)methyl, 3-ethyl-2-[5-(1,2,4-oxadiazolyl)]ethyl, 1-[3-propyl-5-(1,2,4-oxadiazolyl)]ethyl, 3-[5-butyl-3-(1,2,4-oxadiazolyl)]propyl, 4-[3-pentyl-5-(1,2,4-oxadiazolyl)]butyl, 5-[5-hexyl-3-(1,2,4-oxadiazolyl)]pentyl, 6-[3-methyl-5-(1,2,4-oxadiazolyl)]hexyl, 1,1-dimethyl-2-[5-isopropyl-3-(1,2,4-oxadiazolyl)]ethyl, 2-methyl-3-[3-isobutyl-5-(1,2,4-oxadiazolyl)]propyl groups.

Examples of the thiazolydinyl lower alkyl group which may have an oxo group as a substituent on the thiazolydine ring include thiazolydinylalkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolydine ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2,3,4, or 5-)thiazolidinylmethyl, 2-[(2,3,4, or 5-)thiazolidinyl]ethyl, 1-[(2,3,4, or 5-)thiazolidinyl]ethyl, 3-[(2,3,4, or 5-)thiazolidinyl]propyl, 4-[(2,3,4, or 5-)thiazolidinyl]butyl, 5-[(2,3,4, or 5-)thiazolidinyl]pentyl, 6-[(2,3,4, or 5-)thiazolidinyl]hexyl, 1,1-dimethyl-2-[(2,3,4, or 5-)thiazolidinyl]ethyl, 2-methyl-3-[(2,3,4, or 5-)thiazolidinyl]propyl, 2,4-dioxo-5-thiazolidinylmethyl, 2-[2-oxo-(3,4, or 5-)thiazolidinyl]ethyl, 1-[4-oxo-(2,3, or 5-)thiazolidinyl]ethyl, 3-[5-oxo-(2,3, or 4-)thiazolidinyl]propyl, 4-[2,5-dioxo-(3 or 4-)thiazolidinyl]butyl, S-[2,4,5-trioxo-3-thiazolidinyl]pentyl, 6-[4,5-dioxo-(2 or 3-)thiazolidinyl]hexyl, 1,1-dimethyl-2-[2,4-dioxo-(3 or 5-)thiazolidinyl]ethyl, 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propyl, 3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propyl groups.

Examples of the phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include, in addition to the above described phenyl lower alkyl groups, phenylalkyl groups which may have a linear or branched alkylenedioxy group as a substituent on the phenyl ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 3,4-methylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2-(2,3-ethylenedioxyphenyl)ethyl, 1-(3,4-trimethylenedioxyphenyl) ethyl, 3-(2,3-tetramethylenedioxyphenyl)propyl, 4-(3,4-methylenedioxyphenyl)butyl, 5-(2,3-ethylenedioxyphenyl)pentyl, 6-(3,4-trimethylenedioxyphenyl)hexyl, 1,1-dimethyl-2-(2,3-methylenedioxyphenyl)ethyl, 2-methyl-3-(3,4-ethylenedioxyphenyl)propyl groups.

Examples of the lower alkoxycarbonyl lower alkyl group include alkoxycarbonylalkyl groups of which the alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms and the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a methoxycarbonylmethyl group, ethoxycarbonylmethyl group, 2-methoxycarbonylethyl group, 2-ethoxycarbonylmethyl group, 1-ethoxycarbonylethyl group, 3-methoxycarbonylpropyl group, 3-ethoxycarbonylpropyl group, 4-ethoxycarbonylbutyl group, 5-isopropoxycarbonylpentyl group, 6-propoxycarbonylhexyl group, 1,1-dimethyl-2-butoxycarbonylethyl group, 2-methyl-3-tert-butoxycarbonylpropyl group, 2-pentyloxycarbonylethyl group, and hexyloxycarbonylmethyl group.

Examples of the carboxy lower alkyl group include carboxyalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a carboxymethyl group, 2-carboxyethyl group, 1-carboxyethyl group, 3-carboxypropyl group, 4-carboxybutyl group, 5-carboxypentyl group, 6-carboxyhexyl group, 1,1-dimethyl-2-carboxyethyl group, and 2-methyl-3-carboxypropyl group.

Examples of the morpholino substituted lower alkanoyl group include morpholino substituted alkanoyl groups of which the alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as a 2-[(2,3 or 4-)morpholino]acetyl group, 3-[(2,3 or 4-)morpholino]propionyl group, 2-[(2,3 or 4-)morpholino]propionyl group, 4-[(2,3 or 4-)morpholino]butyryl group, 5-[(2,3 or 4-)morpholino]pentanoyl group, 6-[(2,3 or 4-)morpholino]hexanoyl group, 2,2-dimethyl-2-[(2,3 or 4-)morpholino]propionyl group, and 2-methyl-3-[(2,3 or 4-)morpholino]propionyl group.

Examples of the piperazinylcarbonyl lower alkyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylcarbonylalkyl groups which may be substituted on the piperazine ring with 1 to 3 phenylalkyl groups which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, the piperazinylcarbonylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, such as [(1,2, or 3-)piperazinyl]carbonylmethyl, 2-[(1,2, or 3-)piperazinyl]carbonylethyl, 1-[(1,2, or 3-)piperazinyl]carbonylethyl, 3-[(1,2, or 3-)piperazinyl]carbonylpropyl, 4-[(1,2, or 3-)piperazinyl]carbonylbutyl, 5-[(1,2, or 3-)piperazinyl]carbonylpentyl, 6-[(1,2, or 3-)piperazinyl]carbonylhexyl, 1,1-dimethyl-2-[(1,2, or 3-)piperazinyl]carbonylethyl, 2-methyl-3-[(1,2, or 3-)piperazinyl]carbonylpropyl, (4-benzyl-1-piperazinylcarbonyl)methyl, 2-[4-(2-phenylethyl)-1-piperazinylcarbonyl]ethyl, 1-[4-(3-phenylpropyl)-1-piperazinylcarbonyl]ethyl, 3-[4-(4-phenylbutyl)-1-piperazinylcarbonyl]propyl, 4-[4-(5-phenylpentyl)-1-piperazinylcarbonyl]butyl, 5-[4-(6-phenylpropyl)-1-piperazinylcarbonyl]pentyl, 6-(4-benzyl-1-piperazinylcarbonyl)hexyl, 1,1-dimethyl-2-(4-benzyl-1-piperazinylcarbonyl)ethyl, 2-methyl-3-(4-benzyl-1-piperazinylcarbonyl)propyl, [4-(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]methyl, 2-{4-[2-(2,3-ethylenedioxyphenyl)ethyl]-1-piperazinylcarbonyl}ethyl, 1-{4-[3-(3,4-trimethylenedioxyphenyl)propyl]-1-piperazinylcarbonyl}ethyl, 3-{4-[4-(2,3-tetramethylenedioxyphenyl)butyl]-1-piperazinylcarbonyl}propyl, 4-{4-[5-(3,4-methylenedioxyphenyl)pentyl]-1-piperazinylcarbonyl}butyl, 5-{4-[3-(2,3-ethylenedioxyphenyl)propyl]-1-piperazinylcarbonyl}pentyl, 6-[4-(3,4-trimethylenedioxybenzyl)-1-piperazinylcarbonyl]hexyl, 1,1-dimethyl-2-[4-(2,3-tetramethylenedioxybenzyl)-1-piperazinylcarbonyl]ethyl, 2-methyl-3-[4-(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]propyl, (3,4-dibenzyl-1-piperazinylcarbonyl)methyl, (3,4,5-tribenzyl-1-piperazinylcarbonyl)methyl, [2,4-di(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl])methyl, [2,4,6-tri(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]methyl, [3-benzyl-4-(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]methyl groups.

Examples of the piperazinyl lower alkanoyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylalkanoyl groups which may be substituted on the piperazine ring with 1 to 3 phenylalkyl groups which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, the piperazinylalkanoyl groups of which the alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms, such as 2-[(1,2, or 3-)piperazinyl]acetyl, 3-[(1,2, or 3-)piperazinyl]propionyl, 2-[(1,2, or 3-)piperazinyl]propionyl, 4-[(1,2, or 3-)piperazinyl]butyryl, 5-[(1,2, or 3-)piperazinyl]pentanoyl, 6-[(1,2, or 3-)piperazinyl]hexanoyl, 2,2-dimethyl-3-[(1,2, or 3-)piperazinyl]propionyl, 2-methyl-3-[(1,2, or 3-)piperazinyl]propionyl, 2-(4-benzyl-1-piperazinyl)acetyl, 3-[4-(2-phenylethyl)-1-piperazinyl]propionyl, 2-[4-(3-phenylpropyl)-1-piperazinyl]propionyl, 4-[4-(4-phenylbutyl)-1-piperazinyl]butyryl, 5-[4-(5-phenylpentyl)-1-piperazinyl]pentanoyl, 6-[4-(6-phenylpropyl)-1-piperazinyl]hexanoyl, 6-(4-benzyl-1-piperazinyl)hexanoyl, 2,2-dimethyl-3-(4-benzyl-1-piperazinyl)propionyl, 2-methyl-3-(4-benzyl-1-piperazinyl)propionyl, 2-[4-(3,4-methylenedioxybenzyl)-1-piperazinyl])acetyl, 3-{4-[2-(2,3-ethylenedioxyphenyl)ethyl]-1-piperazinyl}propionyl, 2-{4-[3-(3,4-trimethylenedioxyphenyl)propyl]-1-piperazinyl}propionyl, 4-{4-[4-(2,3-tetramethylenedioxyphenyl)butyl]-1-piperazinyl}butyryl, 5-{4-[5-(3,4-methylenedioxyphenyl)pentyl]-1-piperazinyl}pentanoyl, 5-{4-[3-(2,3-ethylenedioxyphenyl)propyl]-1-piperazinyl}pentanoyl, 6-[4-(3,4-trimethylenedioxybenzyl)-1-piperazinyl])hexanoyl, 2,2-dimethyl-3-[4-(2,3-tetramethylenedioxybenzyl)-1-piperazinyl]propionyl, 2-methyl-3-[4-(3,4-methylenedioxybenzyl)-1-piperazinyl]propionyl, 2-(3,4-dibenzyl-1-piperazinyl)acetyl, 2-(3,4,5-tribenzyl-1-piperazinyl)acetyl, 2-[2,4-di(3,4-methylenedioxybenzyl)-1-piperazinyl])acetyl, 2-[2,4,6-tri(3,4-methylenedioxybenzyl)-1-piperazinyl])acetyl, 2[3-benzyl-4-(3,4-methylenedioxybenzyl)-1-piperazinyl])acetyl groups.

Examples of the morpholinocarbonyl substituted lower alkyl group include morpholinocarbonylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2,3, or 4-)morpholino]carbonylmethyl, 2-[(2,3, or 4-)morpholino]carbonylethyl, 1-[(2,3, or 4-)morpholino]carbonylethyl, 3-[(2,3, or 4-)morpholino]carbonylpropyl, 4-[(2,3, or 4-)morpholino]carbonylbutyl, 5-[(2,3, or 4-)morpholino]carbonylpentyl, 6-[(2,3, or 4-)morpholino]carbonylhexyl, 1,1-dimethyl-2-[(2,3, or 4-)morpholino]carbonylethyl, 2-methyl-3-[(2,3, or 4-)morpholino]carbonylpropyl groups.

Examples of the imidazolyl lower alkanoyl group include imidazolylalkanoyl groups of which the alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as a 2-[(1,2,4 or 5-)imidazolyl]acetyl group, 3-[(1,2,4 or 5-)imidazolyl]propionyl group, 2-[(1,2,4 or 5-)imidazolyl]propionyl group, 4-[(1,2,4 or 5-)imidazolyl]butyryl group, 5-[(1,2,4 or 5-)imidazolyl]pentanoyl group, 6-[(1,2,4 or 5-)imidazolyl]hexanoyl group, 2,2-dimethyl-3-[(1,2,4 or 5-)imidazolyl]propionyl group, and 2-methyl-3-[(1,2,4 or 5-)imidazolyl]propionyl group.

Examples of the cycloalkylcarbonyl group include cycloalkylcarbonyl groups of which the cycloalkyl moiety is a cycloalkyl group having 3 to 16 carbon atoms such as a cyclopropylcarbonyl group, cyclobutylcarbonyl group, cyclopentylcarbonyl group, cyclohexylcarbonyl group, cycloheptylcarbonyl group, cyclooctylcarbonyl group, cyclononylcarbonyl group, cyclodecylcarbonyl group, cycloundecylcarbonyl group, cyclododecylcarbonyl group, cyclotridecylcarbonyl group, cyclotetradecylcarbonyl group, cyclopentadecylcarbonyl group, and cyclohexadecylcarbonyl group.

Examples of the amino substituted lower alkanoyl group which may have a lower alkyl group as a substituent include linear or branched alkanoyl groups having 2 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents such as aminoacetyl, 2-aminopropionyl, 3-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl, 6-aminohexanoyl, 2,2-dimethyl-3-aminopropionyl, 2-methyl-3-aminopropionyl, methylaminoacetyl, 2-ethylaminopropionyl, 3-propylaminopropionyl, 3-isopropylaminopropionyl, 4-butylaminobutyryl, 5-pentylaminopentanoyl, 6-hexylaminohexanoyl, dimethylaminoacetyl, 3-diisopropylaminopropionyl, (N-ethyl-N-propylamino)acetyl, 2-(N-methyl-N-hexylamino)acetyl groups.

Examples of the lower alkylene group which may have a hydroxyl group as a substituent include, in addition to the above described lower alkylene groups, linear or branched alkylene groups having 1 to 6 carbon atoms which may have 1 to 3 hydroxyl groups as substituents such as 1-hydroxymethylene, 2-hydroxyethylene, 1-hydroxyethylene, 2-hydroxytrimethylene, 3-hydroxytrimethylene, 1-hydroxytrimethylene, 3-hydroxy-2-methyltrimethylene, 1-hydroxy-2-methyltrimethylene, 3-hydroxy-2,2-dimethyltrimethylene, 1-hydroxy-2,2-dimethyltrimethylene, 3-hydroxy-1-methyltrimethylene, 2-hydroxy-1-methyltrimethylene, 1-hydroxymethylmethylene, hydroxymethylmethylene, 2-hydroxymethyltrimethylene, 2-hydroxymethyl-2-methyltrimethylene, (2-hydroxyethyl)methylene, (1-hydroxyethyl)methylene, 4-hydroxytetramethylene, 2-hydroxytetramethylene, 3-hydroxytetramethylene, 1-hydroxytetramethylene, 5-hydroxypentamethylene, 4-hydroxypentamethylene, 3-hydroxypentamethylene, 2-hydroxypentamethylene, 1-hydroxypentamethylene, 6-hydroxyhexamethylene, 5-hydroxyhexamethylene, 4-hydroxyhexamethylene, 3-hydroxyhexamethylene, 2-hydroxyhexamethylene, 1-hydroxyhexamethylene, 1,2-dihydroxytrimethylene, 2,2,4-trihydroxytetramethylene, 1,2,6-trihydroxyhexamethylene, 3,4,5-trihydroxypentamethylene groups.

Examples of the alkyl group which may have a hydroxyl group as a substituent include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 16 carbon atoms which have 1 to 3 hydroxyl groups as substituents such as a heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, 1-methylhexyl group, hexadecyl group, hydroxymethyl group, 2-hydroxyethyl group, 1-hydroxyethyl group, 3-hydroxypropyl group, 2,3-dihydroxypropyl group, 4-hydroxybutyl group, 1,1-dimethyl-2-hydroxyethyl group, 5,5,4-trihydroxypentyl group, 5-hydroxypentyl group, 6-hydroxyhexyl group, 1-hydroxyisopropyl group, and 2-methyl-3-hydroxypropyl group.

Examples of the hydroxyl group substituted alkyl group include linear or branched alkyl groups having 1 to 16 carbon atoms having 1 to 3 hydroxyl groups as substituents such as a hydroxymethyl group, 2-hydroxyethyl group, 1-hydroxyethyl group, 3-hydroxypropyl group, 2,3-dihydroxypropyl group, 4-hydroxybutyl group, 1,1-dimethyl-2-hydroxyethyl group, 5,5,4-trihydroxypentyl group, 5-hydroxypentyl group, 6-hydroxyhexyl group, 1-hydroxyisopropyl group, and 2-methyl-3-hydroxypropyl group.

Examples of the cycloalkyl group which may have a substituent selected from the group consisting of a hydroxyl group and a lower alkyl group include, in addition to the above described cycloalkyl groups, cycloalkyl groups having 3 to 16 carbon atoms which may have 1 to 3 substituents selected from the group consisting of a hydroxyl group and a linear or branched alkyl group having 1 to 6 carbon atoms such as 2-hydroxycyclopropyl, 3-hydroxycyclobutyl, 3-hydroxycyclopentyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, 3-hydroxycycloheptyl, 4-hydroxycyclooctyl, 5-hydroxycyclononyl, 3-hydroxycyclodecyl, 4-hydroxycycloundecyl, 5-hydroxycyclododecyl, 6-hydroxycyclotridecyl, 7-hydroxycyclotetradecyl, 6-hydroxycyclopentadecyl, 8-hydroxycyclohexadecyl, 2,4-dihydroxycyclohexyl, 2,4,6-trihydroxycyclohexyl, 1-methylcyclopentyl, 2-ethylcyclopropyl, 3-n-propylcyclobutyl, 2-n-butylcyclohexyl, 4-n-pentylcycloheptyl, 4-n-hexylcyclooctyl, 2,3-dimethylcyclohexyl, 2,3,4-trimethylcyclohexyl, 2-methyl-4-hydroxycyclohexyl groups.

Examples of the phenoxy lower alkyl group include phenoxyalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a phenoxymethyl group, 2-phenoxyethyl group, 1-phenoxyethyl group, 3-phenoxypropyl group, 4-phenoxybutyl group, 1,1-dimethyl-2-phenoxyethyl group, 5-phenoxypentyl group, 6-phenoxyhexyl group, 1-phenoxyisopropyl group, and 2-methyl-3-phenoxypropyl group.

Examples of the amino lower alkoxy group which may have a lower alkyl group as a substituent include linear or branched alkoxy groups having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms such as aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy, 4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, 2-diethylaminoethoxy, 2-diisopropylaminoethoxy, (N-ethyl-N-propylamino)methoxy, 2-(N-methyl-N-hexylamino)ethoxy groups.

Examples of the hydroxyl group substituted lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms which have 1 to 3 hydroxyl groups as substituents such as a hydroxymethyl group, l-hydroxyethyl group, 2-hydroxyethyl group, 3-hydroxypropyl group, 2,3-dihydroxypropyl group, 4-hydroxybutyl group, 1,1-dimethyl-2-hydroxyethyl group, 5,5,4-trihydroxypentyl group, 5-hydroxypentyl group, 6-hydroxyhexyl group, 1-hydroxyisopropyl group, and 2-methyl-3-hydroxypropyl group.

Examples of the amino group which may have a lower alkylsulfonyl as a substituent include amino groups which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents such as amino, methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, butylsulfonylamino, tert-butylsulfonylamino, pentylsulfonylamino, hexylsulfonylamino, dimethylsulfonylamino, diethylsulfonylamino, dipropylsulfonylamino, dibutylsulfonylamino, dipentylsulfonylamino, dihexylsulfonylamino, N-methylsulfonyl-N-ethylsulfonylamino, N-ethylsulfonyl-N-propylsulfonylamino, N-methylsulfonyl-N-butylsulfonylamino, N-methylsulfonyl-N-hexylsulfonylamino groups.

Examples of the lower alkynyl group include linear or branched alkynyl groups having 2 to 6 carbon atoms include an ethynyl group, 2-propynyl group, 2-butynyl group, 3-butynyl group, 1-methyl-2-propynyl group, 2-pentynyl group, and 2-hexynyl group.

Examples of the anilino group which may have a halogen atom as a substituent on the phenyl ring include anilino groups which may have 1 to 3 halogen atoms as substituents on the phenyl ring such as anilino, 2-fluoroanilino, 3-fluoroanilino, 4-fluoroanilino, 2-bromoanilino, 3-bromoanilino, 4-bromoanilino, 2-iodoanilino, 3-iodoanilino, 4-iodoanilino, 2,3-dibromoanilino, 2,4-diiodoanilino, 2,5-difluoroanilino, 2,6-dichloroanilino, 2,4,6-trichloroanilino, 2,6-difluoroanilino, 3,5-difluoroanilino, 2,6-difluoroanilino, 2-chloroanilino, 3-chloroanilino, 4-chloroanilino, 2,3-dichloroanilino, 2,4-dichloroanilino, 2,5-dichloroanilino, 3,4-dichloroanilino, 2,6-dichloroanilino, 3,5-dichloroanilino, 2,4,6-trifluoroanilino, 2,4-difluoroanilino, 3,4-difluoroanilino groups.

Examples of the piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring include piperazinyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperazine ring such as a (1-,2- or 3-)piperazinyl group, 4-methyl-(1-,2- or 3-)piperazinyl group, 2,3-dimethyl-(1 or 5-)piperazinyl group, and 2,3,4-trimethyl-(1-,5- or 6-)piperazinyl group.

Examples of the pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring include pyrrolidinyl groups which may have 1 or 2 oxo groups as substituents on the pyrrolidine ring such as a (1-,2- or 3-)pyrrolidinyl group, 2-oxo-(1-,3-,4- or 5-)pyrrolidinyl group, 3-oxo-(1-,2-,4- or 5-)pyrrolidinyl group, 2,3-dioxo-(1-,4- or 5-)pyrrolidinyl group, and 2,5-dioxo-(1-,3- or 4-)pyrrolidinyl group.

Examples of the phenyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy groups which may have a halogen atom as a substituent; a halogen atom; an amino lower alkoxy group which may have a lower alkyl group as a substituent; a hydroxyl group substituted lower alkyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group which may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group which may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring; a pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group include phenyl groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms; a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms; a halogen atom; an aminoalkoxy group of which the alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms and which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atom as substituents; a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 hydroxyl groups as substituents; a phenylalkyl group of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms; a linear or branched alkynyl group having 2 to 6 carbon atoms; an amino group which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents; a linear or branched alkylthio group having 1 to 6 carbon atoms; a cycloalkyl group having 3 to 16 carbon atoms; a phenylthio group; an adamantyl group; an anilino group which may have 1 to 3 halogen atoms as substituents on the phenyl ring; a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms; a piperazinyl group which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperazine ring; a pyrrolidinyl group which may have 1 or 2 oxo groups as substituents on the pyrrolidine ring; an amino group which may have 1 or 2 linear or branched alkanoyl groups having 2 to 6 carbon atoms; a cyano group; and a phenoxy group such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2-isopropylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-(bromomethoxy)phenyl, 3-(2-chloroethoxy)phenyl, 4-(2,3-dichloropropoxy)phenyl, 4-(4-fluorobutoxy)phenyl, 3-(5-chloropentyloxy)phenyl, 4-(5-bromohexyloxy)phenyl, 4-(5,6-dibromohexyloxy)phenyl, 3,4-di(trifluoromethoxy)phenyl, 3,4-di(4,4,4-trichlorobutoxy)phenyl, 2,4-di(3-chloro-2-methoxypropyl)phenyl, 2,5-di(3-chloropropoxy)phenyl, 2,6-di(2,2,2-trifluoroethoxy)phenyl, 3,4,5-tri(trifluoromethoxy)phenyl, 4-(2,2,2-trichloroethoxy)phenyl, 2-methyl-4-trifluoromethoxyphenyl, 3-ethyl-4-trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-methyl-3-trifluoromethoxy-4-trifluoromethoxyphenyl, 2-phenoxyphenyl, 3-phenoxyphenyl, 4-phenoxyphenyl, 2,3-diphenoxyphenyl, 3,4-diphenoxyphenyl, 2,6-diphenoxyphenyl, 3,4,5-triphenoxyphenyl, 2-methyl-4-phenoxyphenyl, 3-ethyl-4-phenoxyphenyl, 2-methoxy-4-phenoxyphenyl, 3-ethoxy-4-phenoxyphenyl, 2-methyl-3-phenoxy-4-trifluoromethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,4,6-trichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,5-difluorophenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,4,6-trifluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2,3-dibromophenyl, 2,4-diiodophenyl, 4-methylthiophenyl, 4-cyclohexylphenyl, 4-chloro-2-anilinophenyl, 2-(4-chloroanilino)-5-ethoxycarbonylphenyl, 4-[2-(N,N-diethylamino)ethoxy]phenyl, 4-(4-methyl-1-piperazinyl)phenyl, 4-(2-oxo-1-pyrrolidinyl)phenyl, 4-methylsulfonylaminophenyl, 4-(2-hydroxyethyl)phenyl, 4-benzylphenyl, 4-ethinylphenyl, 4-phenylthiophenyl, 4-(1-adamantyl)phenyl, 5-acetylamino-2-chlorophenyl, 3-cyanophenyl, 2-cyanophenyl, 4-cyanophenyl, 2-propanoylaminophenyl, 3,4-dicyanophenyl, 3,4,5-tricyanophenyl groups.

Examples of the phenyl lower alkyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group include, in addition to the above described phenyl lower alkyl groups, phenylalkyl groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkyl group having 1 to 6 carbon atoms, and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, such as 4-fluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-(2-fluorophenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 3,4-dibromobenzyl, 3,4-diiodobenzyl, 2,4-difluorobenzyl, 2,5-dichlorobenzyl, 2,6-dichlorobenzyl, 3,4,5-trifluorobenzyl, 3-(4-chlorophenyl)propyl, 1-(2-bromophenyl)ethyl, 4-(3-fluorophenyl)butyl, 5-(4-iodophenyl)pentyl, 6-(4-chlorophenyl)hexyl, 1,1-dimethyl-2-(3-fluorophenyl)ethyl, 2-methyl-3-(4-chlorophenyl)propyl, 2-methylbenzyl, 2-(3-methylphenyl)ethyl, 3-(4-methylphenyl)propyl, 1-(2-ethylphenyl)ethyl, 4-(3-ethylphenyl)butyl, 5-(4-ethylphenyl)pentyl, 6-(4-isopropylphenyl)hexyl, 1,1-dimethyl-2-(3-butylphenyl)ethyl, 2-methyl-3-(4-pentylphenyl)propyl, 4-hexylbenzyl, 3,4-dimethylbenzyl, 3,4-diethylbenzyl, 2,4-dimethylbenzyl, 2,5-dimethylbenzyl, 2,6-dimethylbenzyl, 3,4,5-trimethylbenzyl, 2-methoxybenzyl, 2-(2-methoxyphenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 4-methoxybenzyl, 1-(2-ethoxyphenyl)ethyl, 3-(3-ethoxyphenyl)propyl, 4-(4-ethoxyphenyl)butyl, 5-(4-isopropoxyphenyl)pentyl, 6-(3-butoxyphenyl)hexyl, 1,1-dimethyl-2-(4-pentyloxyphenyl)ethyl, 2-methyl-3-(4-hexyloxyphenyl)propyl, 3,4-dimethoxybenzyl, 3,4-diethoxybenzyl, 2,4-dimethoxybenzyl, 2,5-dimethoxybenzyl, 2,6-dimethoxybenzyl, 3,4,5-trimethoxybenzyl, 2-trifluoromethoxybenzyl, 3-trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2-[2-(bromomethoxy)phenyl]ethyl, 1-[3-(2-chloroethoxy)phenyl]ethyl, 3-[4-(2,3-dichloropropoxy)phenyl]propyl, 4-[4-(4-fluorobutoxy)phenyl]butyl, 5-[3-(5-chloropentyloxy)phenyl]pentyl, 6-[4-(5-bromohexyloxy)phenyl]hexyl, 1,1-dimethyl-2-[4-(5,6-dibromohexyloxy)phenyl]ethyl, 3,4-di(trifluoromethoxy)benzyl, 3,4-di(4,4,4-trichlorobutoxy)benzyl, 2,4-di(3-chloro-2-methoxypropyl)benzyl, 2,5-di(3-chloropropoxy)benzyl, 2,6-di(2,2,2-trifluoroethoxy)benzyl, 3,4,5-tri(trifluoromethoxy)benzyl, 4-(2,2,2-trichloroethoxy)benzyl, 2-methyl-4-trifluoromethoxybenzyl, 3-ethyl-4-trichloromethoxybenzyl, 2-methoxy-4-trifluoromethoxybenzyl, 3-ethoxy-4-trichloromethoxybenzyl, 2-methyl-3-trifluoromethoxy-4-trifluoromethoxybenzyl, 2-chloro-3-methylbenzyl, 4-fluoro-2-trifluoromethoxybenzyl, 3-chloro-2-methyl-4-methoxybenzyl groups.

Examples of the phenyl lower alkyl group which has a lower alkylenedioxy group as a substituent on the phenyl ring include phenylalkyl groups which has a linear or branched alkylenedioxy group having 1 to 4 carbon atoms on the phenyl ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a 3,4-methylenedioxybenzyl group, 3,4-trimethylenedioxybenzyl group, 2-(2,3-ethylenedioxyphenyl)ethyl group, 1-(3,4-trimethylenedioxyphenyl)ethyl group, 3-(2,3-tetramethylenedioxyphenyl)propyl group, 4-(3,4-methylenedioxyphenyl)butyl group, 5-(2,3-ethylenedioxyphenyl)pentyl group, 6-(3,4-trimethylenedioxyphenyl)hexyl group, 1,1-dimethyl-2-(2,3-methylenedioxyphenyl)ethyl group, and 2-methyl-3-(3,4-ethylenedioxyphenyl)propyl group.

Examples of the amino group which may have a lower alkanoyl group as a substituent include which may have a linear or branched alkanoyl group having 1 to 6 carbon atoms as a substituent such as an amino group, N-acetylamino group, N-formylamino group, N-propionylamino group, N-butyrylamino group, N-isobutyrylamino group, N-pentanoylamino group, N-tert-butylcarbonylamino group, and N-hexanoylamino group.

Examples of the 1,2,3,4-tetrahydroquinolyl group which may have, on the tetrahydroquinoline ring, 1 to 3 substituents selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group include 1,2,3,4-tetrahydroquinolyl groups which may have, on the tetrahydroquinoline ring, 1 to 3 substituents selected from the group consisting of an oxo group, a linear or branched alkoxy group having 1 to 6 carbon atoms, and a linear or branched alkylenedioxy group having 1 to 4 carbon atoms such as (1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl, 2-oxo-(1,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl, 2-oxo-6,7-methylenedioxy-(1,3,4,5, or 8-)1,2,3,4-tetrahydroquinolyl, 4-oxo-(1,2,3,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl, 2,4-dioxo-(1,3,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl, 2,4-dioxo-6,7-methylenedioxy-(1,3,5, or 8-)1,2,3,4-tetrahydroquinolyl, 5,6-ethylenedioxy-(1,2,3,4,7, or 8-)1,2,3,4-tetrahydroquinolyl, 7,8-trimethylenedioxy-(1,2,3,4,5, or 6-)1,2,3,4-tetrahydroquinolyl, 6,7-tetramethylenedioxy-(1,2,3,4,5, or 8-)1,2,3,4-tetrahydroquinolyl, 5-methoxy-2-oxo-(1,3,4,6,7, or 8-)1,2,3,4-tetrahydroquinolyl, 2-oxo-6,7-ethylenedioxy-(1,3,4,5, or 8-)1,2,3,4-tetrahydroquinolyl groups.

Examples of the cycloalkyl lower alkyl group include cycloalkylalkyl groups having 3 to 16 carbon atoms of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a cyclopropylmethyl group, cyclohexylmethyl group, 2-cyclopropylethyl group, 1-cyclobutylethyl group, 3-cyclopentylpropyl group, 4-cyclohexylbutyl group, 5-cycloheptylpentyl group, 6-cyclooctylhexyl group, 1,1-dimethyl-2-cyclononylethyl group, 2-methyl-3-cyclodecylpropyl group, cycloundecylmethyl group, 2-cyclododecylethyl group, 1-cyclotridecylethyl group, 3-cyclotetradecylpropyl group, 4-cyclopentadecylbutyl group, and 5-cyclodecylpentyl group.

Examples of the pyridyl lower alkyl group include pyridylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a (2,3 or 4-)pyridylmethyl group, 2-[(2,3 or 4-)pyridyl]ethyl group, 1-[(2,3 or 4-)pyridyl]ethyl group, 3-[(2,3 or 4-)pyridyl]propyl group, 4-[(2,3 or 4-)pyridyl]butyl group, 1,1-dimethyl-2-[(2,3 or 4-)pyridyl]ethyl group, 5-[(2,3 or 4-)pyridyl]pentyl group, 6-[(2,3 or 4-)pyridyl]hexyl group, 1-[(2,3 or 4-)pyridyl]isopropyl group, and 2-methyl-3-[(2,3 or 4-)pyridyl]propyl group.

Examples of the amino group substituted lower alkyl group which may have a substituent selected from the group consisting of a lower alkyl group and a lower alkanoyl group include linear or branched alkyl groups having 1 to 6 carbon atoms which has an amino group which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkanoyl group having 1 to 6 carbon atoms such as aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diisopropylaminoethyl, (N-ethyl-N-propylamino)methyl, 2-(N,N-dimethylamino)ethyl, 2-(N-methyl-N-hexylamino)ethyl, formylaminomethyl, acetylaminomethyl, 1-propionylaminoethyl, 2-acetylaminoethyl, 3-butyrylaminopropyl, 4-pentanoylaminobutyl, 5-hexanoylaminopentyl, 6-acetylaminohexyl, N-methyl-N-acetylaminomethyl, 2-(N-ethyl-N-propanoylamino)ethyl, (N-ethyl-N-butyrylamino)methyl, 2-(N-methyl-N-hexanoylamino)ethyl, 3-(N,N-dimethylamino)propyl groups.

Examples of the lower alkoxy lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms which have a linear or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as a methoxymethyl group, 1-ethoxyethyl group, 2-methoxyethyl group, 2-propoxyethyl group, 3-isopropoxypropyl group, 4-butoxybutyl group, 5-pentyloxypentyl group, 6-hexyloxyhexyl group, 1,1-dimethyl-2-methoxyethyl group, 2-methyl-3-ethoxypropyl group, and 3-methoxypropyl group.

Examples of the 1,2,3,4-tetrahydroisoquinolylcarbonyl substituted lower alkyl group include 1,2,3,4-tetrahydroisoquinolylcarbonyl-alkyl groups of which the alkyl moiety is a linear or branched alkyl group such as (1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroisoquinolylcarbonylmethyl, 2-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroisoquinolyl-carbonyl]ethyl, 1-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]ethyl, 3-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroisoquinolyl-carbonyl]propyl, 4-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]butyl, 1,1-dimethyl-2-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]ethyl, 5-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroisoquinolyl-carbonyl]pentyl, 6-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]hexyl, 1-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroisoquinolyl-carbonyl]isopropyl, 2-methyl-3-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]propyl groups.

Examples of the piperidinylcarbonyl group which may have, on the piperidine ring, a substituent selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, and a furyl lower alkyl group include piperidinylcarbonyl groups which may have, on the piperidine ring, 1 to 3 substituents selected from the group consisting of an alkoxycarbonyl group of which the alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms, a phenylalkyl group of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, and a furylalkyl group of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1,2,3, or 4-)piperidinylcarbonyl, 1-benzyl-(2,3, or 4-)piperidinylcarbonyl, 1-(2 or 3-)furylmethyl-(2,3, or 4-)piperidinylcarbonyl, 1-(2-phenylethyl)-(2,3, or 4-)piperidinylcarbonyl, 1-{2-[(1 or 2-)furyl]ethyl}-(2,3, or 4-)piperidinyl-carbonyl, 1-(1-phenylethyl)-(2,3, or 4-)piperidinyl-carbonyl, 1-{3-[(1 or 2-)furyl]propyl]}-(2,3, or 4-)piperidinylcarbonyl, 1-(3-phenylpropyl)-(2,3, or 4-)piperidinylcarbonyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2,3, or 4-)piperidinylcarbonyl, 1-(4-phenylbutyl)-(2,3, or 4-)piperidinylcarbonyl, 1-{4-[(1 or 2-)furyl]-butyl]}-(2,3, or 4-)piperidinylcarbonyl, 1-(5-phenylpentyl)-(2,3, or 4-)piperidinylcarbonyl, 1-{5-[(1 or 2-)furyl]pentyl]}-(2,3, or 4-)piperidinyl-carbonyl, 1-(6-phenylhexyl)-(2,3, or 4-)piperidinyl-carbonyl, 1-{6-[(1 or 2-)furyl]hexyl]}-(2,3, or 4-)piperidinylcarbonyl, 1,2-dibenzyl-(3,4,5, or 6-)piperidinylcarbonyl, 1,3-di(1 or 2-)furylmethyl-(2,4,5, or 6-)piperidinylcarbonyl, 1,3,5-tribenzyl-(2,4, or 6-)piperidinylcarbonyl, 1,2,6-tri(1 or 2-)furylmethyl-(3,4, or 5-)piperidinylcarbonyl, 1-benzyl-3-(1 or 2-)furylmethyl-(2,4,5, or 6-)piperidinylcarbonyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2,3, or 4-)piperidinylcarbonyl, 1-methoxycarbonyl-(2,3, or 4-)piperidinylcarbonyl, 1-ethoxycarbonyl-(2,3, or 4-)piperidinylcarbonyl, 1-propoxycarbonyl-(2,3, or 4-)piperidinylcarbonyl, 1-butoxycarbonyl-(2,3, or 4-)piperidinylcarbonyl, 1-tert-butoxycarbonyl-(2,3, or 4-)piperidinylcarbonyl, 1-pentyloxycarbonyl-(2,3, or 4-)piperidinylcarbonyl, 1-hexyloxycarbonyl-(2,3, or 4-)piperidinylcarbonyl, 1,2-dimethoxycarbonyl-(3,4,5, or 6-)piperidinylcarbonyl, 1,2,6-triethoxycarbonyl-(3,4, or 5-)piperidinylcarbonyl, 1-(1 or 2-)furylmethyl-3-tert-butoxycarbonyl-(3,4,5, or 6-)piperidinyl-carbonyl, 1-benzyl-2-methoxycarbonyl-(2,4,5, or 6-)piperidinylcarbonyl, 1-(1 or 2-)furylmethyl-2,4-dimethoxycarbonyl-(3,5, or 6-)piperidinylcarbonyl groups.

Examples of the thiazolidinyl lower alkanoyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinylalkanoyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and of which the alkanoyl moiety is a linear or branched alkanoyl group having 1 to 6 carbon atoms such as 2-[(2,3,4, or 5-)thiazolidinyl]acetyl, 3-[(2,3,4, or 5-)thiazolidinyl]propionyl, 2-[(2,3,4, or 5-)thiazolidinyl]propionyl, 4-[(2,3,4, or 5-)thiazolidinyl]butyryl, 5-[(2,3,4, or 5-)1,2,4-thiazolidinyl]pentanoyl, 6-[(2,3,4, or 5-)thiazolidinyl]hexanoyl, 2,2-dimethyl-3-[(2,3,4, or 5-)thiazolidinyl]propionyl, 2-methyl-3-[(2,3,4, or 5-)thiazolidinyl]propionyl, 2,4-dioxo-(3 or 5-)thiazolidinylacetyl, 3-[2-oxo-(3,4, or 5-)thiazolidinyl]propionyl, 2-[4-oxo-(2,3, or 5-)thiazolidinyl]propionyl, 4-[5-oxo-(2,3, or 4-)thiazolidinyl]butyryl, 5-[2,5-dioxo-(3 or 4-)thiazolidinyl]pentanoyl, 6-[2,4,5-trioxo-3-thiazolidinyl]hexanoyl, 2-[4,5-dioxo-(2 or 3-)thiazolidinyl]acetyl, 2,2-dimethyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl, 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl groups.

Examples of the piperidinyl group which may be substituted on the piperidine ring with a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group and a furyl lower alkyl group include piperidinyl groups which may be substituted on the piperidine ring with 1 to 3 groups selected from the group consisting of an alkoxycarbonyl group of which the alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms, a phenylalkyl group of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkyl group having 1 to 6 carbon atoms, a benzoyl group, and a furylalkyl group of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1,2,3, or 4-)piperidinyl, 1-benzyl-(2,3, or 4-)piperidinyl, 1-(2 or 3-)furylmethyl-(2,3, or 4-)piperidinyl, 1-(2-phenylethyl)-(2,3, or 4-)piperidinyl, 1-{2-[(1 or 2-)furyl]ethyl}-(2,3, or 4-)piperidinyl, 1-(1-phenylethyl)-(2,3, or 4-)piperidinyl, 1-{3-[(1 or 2-)furyl]propyl]}-(2,3, or 4-)piperidinyl, 1-(3-phenylpropyl)-(2,3, or 4-)piperidinyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2,3, or 4-)piperidinyl, 1-(4-phenylbutyl)-(2,3, or 4-)piperidinyl, 1-{4-[(1 or 2-)furyl]butyl]}-(2,3, or 4-)piperidinyl, 1-(5-phenylpentyl)-(2,3, or 4-)piperidinyl, 1-{5-[(1 or 2-)furyl]pentyl]}-(2,3, or 4-)piperidinyl, 1-(6-phenylhexyl)-(2,3, or 4-)piperidinyl, 1-{6-[(1 or 2-)furyl]hexyl]}-(2,3, or 4-)piperidinyl, 1,2-dibenzyl-(3,4,5, or 6-)piperidinyl, 1,3-di(1 or 2-)furylmethyl-(2,4,5, or 6-)piperidinyl, 1,3,5-tribenzyl-(2,4, or 6-)piperidinyl, 1,2,6-tri(1 or 2-)furylmethyl-(3,4, or 5-)piperidinyl, 1-benzyl-3-(1 or 2-)furylmethyl-(2,4,5, or 6-)piperidinyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2,3, or 4-)piperidinyl, 1-benzoyl-(2,3, or 4-)piperidinyl, 1,2-dibenzoyl-(3,4,5, or 6-)piperidinyl, 1,3,5-tribenzoyl-(2,4, or 6-)piperidinyl, 1-methyl-(2,3, or 4-)piperidinyl, 1-ethyl-(2,3, or 4-)piperidinyl, 1-propyl-(2,3, or 4-)piperidinyl, 1-isopropyl-(2,3, or 4-)piperidinyl, 1-butyl-(2,3, or 4-)piperidinyl, 1-isobutyl-(2,3, or 4-)piperidinyl, 1-tert-butyl-(2,3, or 4-)piperidinyl, 1-pentyl-(2,3, or 4-)piperidinyl, 1-hexyl-(2,3, or 4-)piperidinyl, 1,2-dimethyl-(3,4,5, or 6-)piperidinyl, 1,2,6-trimethyl-(3,4, or 5-)piperidinyl, 1-methyl-3-benzyl-(3,4,5, or 6-)piperidinyl, 1-benzoyl-2-methyl-(2,4,5, or 6-)piperidinyl, 1-(1 or 2-)furylmethyl-2,4-dimethyl-(3,5, or 6-)piperidinyl, 1-methoxycarbonyl-(2,3, or 4-)piperidinyl, 1-ethoxycarbonyl-(2,3, or 4-)piperidinyl, 1-propoxycarbonyl-(2,3, or 4-)piperidinyl, 1-butoxycarbonyl-(2,3, or 4-)piperidinyl, 1-tert-butoxycarbonyl-(2,3, or 4-)piperidinyl, 1-pentyloxycarbonyl-(2,3, or 4-)piperidinyl, 1-hexyloxycarbonyl-(2,3, or 4-)piperidinyl, 1,2-dimethoxycarbonyl-(3,4,5, or 6-)piperidinyl, 1,2,6-triethoxycarbonyl-(3,4, or 5-)piperidinyl, 1-methyl-3-tert-butoxycarbonyl-(3,4,5, or 6-)piperidinyl, 1-benzoyl-2-methoxycarbonyl-(2,4,5, or 6-)piperidinyl, 1-(1 or 2-)furylmethyl-2,4-dimethoxycarbonyl-(3,5, or 6-)piperidinyl, 1-benzyl-2,4-dimethoxycarbonyl-(3,5, or 6-)piperidinyl groups.

Examples of the carbonyl lower alkyl group substituted with a group:


(hereinafter called A group) include A group substituted carbonylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as an A group substituted carbonylmethyl group, 2-A group substituted carbonylethyl group, 1-A group substituted carbonylethyl group, 3-A group substituted carbonylpropyl group, 4-A group substituted carbonylbutyl group, 1,1-dimethyl-2-A group substituted carbonylethyl group, 5-A group substituted carbonylpentyl group, 6-A group substituted carbonylhexyl group, 1-A group substituted carbonylisopropyl group, and 2-methyl-3-A group substituted carbonylpropyl group.

Examples of the carbonyl lower alkyl group substituted with a group:


wherein R34 is an oxo group or phenyl group, and d is an integer of 0 to 3 (hereinafter called B group), B group substituted carbonylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a B group substituted carbonylmethyl group, 2-B group substituted carbonylethyl group, 1-B group substituted carbonylethyl group, 3-B group substituted carbonylpropyl group, 4-B group substituted carbonylbutyl group, 1,1-dimethyl-2-B group substituted carbonylethyl group, 5-B group substituted carbonylpentyl group, 6-B group substituted carbonylhexyl group, 1-B group substituted carbonylisopropyl group, and 2-methyl-3-B group substituted carbonylpropyl group.

Examples of the pyrrolidinyl lower alkyl group include pyrrolidinylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a (1-,2-, or 3-)pyrrolidinylmethyl group, 2-[(1-,2-, or 3-)pyrrolydinyl]ethyl group, 1-[(1-,2-, or 3-)pyrrolydinyl]ethyl group, 3-[(1-,2-, or 3-)pyrrolydinyl]propyl group, 4-[(1-,2-, or 3-)pyrrolydinyl]butyl group, 5-[(1-, 2-, or 3-)pyrrolydinyl]pentyl group, 6-[(1-,2-, or 3-)pyrrolydinyl]hexyl group, 1,1-dimethyl-2-[(1-,2-, or 3-)pyrrolydinyl]ethyl group, and 2-methyl-3-[(1-,2-, or 3-)pyrrolydinyl]propyl group.

Examples of the morpholino lower alkyl group include morpholinoalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a (2-,3- or 4-)morpholinomethyl group, 2-[(2-,3- or 4-)morpholino]ethyl group, 1-[(2-,3- or 4-)morpholino]ethyl group, 3-[(2-,3- or 4-)morpholino]propyl group, 4-[(2-,3- or 4-)morpholino]butyl group, 5-[(2-,3- or 4-)morpholino]pentyl group, 6-[(2-,3- or 4-)morpholino]hexyl group, 1,1-dimethyl-2-[(2-,3- or 4-)morpholino]ethyl group, and 2-methyl-3-[(2-,3- or 4-)morpholino]propyl group.

Examples of the phenyl lower alkenyl group include phenylalkenyl groups of which the alkenyl moiety is a linear or branched alkenyl group having 2 to 6 carbon atoms and which have 1 to 3 double bonds such as a styryl group, 3-phenyl-2-propenyl group (trivial name: cinnamyl group), 4-phenyl-2-butenyl group, 4-phenyl-3-butenyl group, 5-phenyl-4-pentenyl group, 5-phenyl-3-pentenyl group, 6-phenyl-5-hexenyl group, 6-phenyl-4-hexenyl group, 6-phenyl-3-hexenyl group, 4-phenyl-1,3-butadienyl group, and 6-phenyl-1,3,5-hexatrienyl group.

Examples of the anilinocarbonyl lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring include anilinocarbonylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the phenyl ring such as anilinocarbonylmethyl, 2-anilinocarbonylethyl, 1-anilinocarbonylethyl, 3-anilinocarbonylpropyl, 4-anilinocarbonylbutyl, 5-anilinocarbonylpentyl, 6-anilinocarbonylhexyl, 1,1-dimethyl-2-anilinocarbonylethyl, 2-methyl-3-anilinocarbonylpropyl, (4-methylanilinocarbonyl)methyl, 2-(3-methylanilinocarbonyl)ethyl, 3-(4-methylanilinocarbonyl)propyl, 1-(2-ethylanilinocarbonyl)ethyl, 4-(3-ethylanilinocarbonyl)butyl, 5-(4-ethylanilinocarbonyl)pentyl, 6-(4-isopropylanilinocarbonyl)hexyl, 1,1-dimethyl-2-(3-butylanilinocarbonyl)ethyl, 2-methyl-3-(4-pentylanilinocarbonyl)propyl, 4-hexylanilinocarbonylmethyl, 3,4-dimethylanilinocarbonylmethyl, 3,4-diethylanilinocarbonylmethyl, 2,4-dimethylanilinocarbonylmethyl, 2,5-dimethylanilinocarbonylmethyl, 2,6-dimethylanilinocarbonylmethyl, 3,4,5-trimethylanilinocarbonylmethyl groups.

Examples of the piperazinyl lower alkyl group which may have, on the piperazine ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a phenylalkyl group which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1-,2-, or 3-)piperazinyl]methyl, 2-[(1-,2-, or 3-)piperazinyl]ethyl, 1-[(1-,2-, or 3-)piperazinyl]ethyl, 3-[(1-,2-, or 3-)piperazinyl]propyl, 4-[(1-,2-, or 3-)piperazinyl]butyl, 5-[(1-,2-, or 3-)piperazinyl]pentyl, 6-[(1-,2-, or 3-)piperazinyl]hexyl, 1,1-dimethyl-2-[(1-,2-, or 3-)piperazinyl]ethyl, 2-methyl-3-[(1-,2-, or 3-)piperazinyl]propyl, [1-methyl-(2-,3-, or 4-)piperazinyl]methyl, 2-[1-ethyl-(2-,3-, or 4-)piperazinyl]ethyl, 1-[4-propyl-(1-,2-, or 3-)piperazinyl]ethyl, 3-[3-isopropyl-(1-,2-,4-, 5-, or 6-)piperazinyl]propyl, 4-[2-butyl-(1-, 3,4-, 5-, or 6-)piperazinyl]butyl, 5-[1-isobutyl-(2-,3-, or 4-)piperazinyl]pentyl, 3-[4-methyl-(1-, 2-, or 3-)piperazinyl]propyl, 6-[l-tert-butyl-(2-,3-, or 4-)piperazinyl]hexyl, 1,1-dimethyl-2-[4-pentyl-(1-, 2-, or 3-)piperazinyl]ethyl, [1,2-dimethyl-(3-,4-, 5-, or 6-)piperazinyl]methyl, [1,2,6-trimethyl-(3-,4-, or 5-)piperazinyl]methyl, 2-[4-(3,4-methylenedioxybenzyl)-(1-,2-, or 3-)piperazinyl]ethyl groups.

Examples of the amidino lower alkyl group which may have a lower alkyl group as a substituent include amidinoalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms such as an amidinomethyl group, 2-amidinoethyl group, 1-amidinoethyl group, 3-amidinopropyl group, 4-amidinobutyl group, 5-amidinopentyl group, 6-amidinohexyl group, 1,1-dimethyl-2-amidinoethyl group, 2-methyl-3-amidinopropyl group, N,N-dimethylamidinomethyl group, 2-(N,N-dimethylamidino)ethyl group, 1-(N-methylamidino)ethyl group, 3-(N-ethylamidino)propyl group, 4-(N-n-propylamidino)propyl group, 5-(N-n-pentylamidino)pentyl group, 6-(N-n-hexylamidino)hexyl group, and (N-methyl-N-ethylamidino)methyl group.

Examples of the carbazolyl group which may have a lower alkyl group as a substituent on the carbazole ring include carbazolyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the carbazole ring such as (1-,2-, 3-, or 4-)carbazolyl, 9-methyl-(1-,2-, 3-, or 4-)carbazolyl, 9-ethyl-(1-,2-, 3-, or 4-)carbazolyl, 1-ethyl-(2-,3-,4-,5-,6-,7-,8-, or 9-)carbazolyl, 2-n-propyl-(1-,3-,4-, 5-,6-,8-, or 9-)carbazolyl, 3-n-butyl-(1-,2-,4-,5-,6-,7-,8-, or 9-)carbazolyl, 4-n-pentyl-(1-,2-,3-,5-,6-,7-,8-, or 9-)carbazolyl, 5-n-hexyl-(1-,2-,3-,4-,6-,7-,8-, or 9-)carbazolyl, 6,9-dimethyl-(1-,2-,3-,4-,5-,7-, or 8-)carbazolyl, 1,7,8-trityl-(2-,3-,4-,5-,6-,7-,8-, or 9-)carbazolyl groups.

Examples of the amidino group which may have a lower alkyl group as a substituent include amidino groups which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents such as an amidino group, N,N-dimethylamidino group, N-methylamidino group, N-ethylamidino group, N-n-propylamidino group, N-n-butylamidino group, N-n-pentylamidino group, N-n-hexylamidino group, N,N-diethylamidino group, and N-methyl-N-ethylamidino group.

Examples of the 5- to 7-membered saturated heterocyclic group formed by binding R36 and R37 each other, together with nitrogen atoms bound to them, through or not through a nitrogen atom, an oxygen atom or a sulfur atom, include a pyrrolidinyl group, piperidinyl group, piperazinyl group, morpholino group, thiomorpholino group, and homopiperazinyl group.

Examples of the 5- to 10-membered saturated or unsaturated heterocyclic group formed by binding R14 and R15 each other, together with nitrogen atoms bound to them, through or not through a nitrogen atom, an oxygen atom or a sulfur atom, include 1,2,3,4,5,6-hexahydropyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, homopiperazinyl, homopiperidinyl, thiazolidinyl, 1,2,5,6-tetrahydropyridyl, pyrrolyl, pyrazolyl, imidazolyl, 2-pyrrolinyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl, pyrazolidinyl, 1,2-dihydropyridyl, 1,2-dihydroquinolyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 1,2-dihydroisoquinolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 3,4-dihydro-2H-1,4-benzoxadinyl, 3,4-dihydro-2H-1,4-benzothiazolidinyl, 1,4-benzothiazinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,2,3,4-tetrahydrocinnolinyl, 1,2,3,4-tetrahydrophthalazinyl, 1,2,3,4-tetrahydroquinazolinyl, 1,2-dihydroquinoxalinyl, 3,4-dihydroquinoxalinyl, 1,4-dihydroquinoxalinyl, 1,2-dihydrocinnolinyl, 1,2-dihydrophthalazinyl, 3,4-dihydrophthalazinyl, 1,2-dihydroquinazolinyl, 3,4-dihydroquinazolinyl, indazolyl, indazolinyl, 6-azabicyclo[3,2,1]octyl, 3-aza-spiro[5,5]undecyl, thiazolidinyl groups.

Examples of the phenyl lower alkoxy group include phenylalkoxy groups of which the alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms such as a benzyloxy group, 2-phenylethoxy group, 1-phenylethoxy group, 3-phenylpropoxy group, 4-phenylbutoxy group, 5-phenylpentyloxy group, 6-phenylhexyloxy group, 1,1-dimethyl-2-phenylethoxy group, and 2-methyl-3-phenylpropoxy group.

Examples of the phenyl substituted lower alkyl group which has 1 or 2 phenyl groups which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy groups; and which may have a pyridyl group on the lower alkyl group include, in addition to the above described phenyl lower alkyl groups, phenyl substituted alkyl groups which have 1 or 2 phenyls which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a linear or branched alkanoyl group having 1 to 6 carbon atoms, an amino group which may have 1 or 2 linear or branched alkanoyl groups having 1 to 6 carbon atoms as substituents, a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, a phenyl group, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a phenylalkoxy groups of which the alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms, a hydroxy group, and a linear or branched alkylenedioxy group having 1 to 4 carbon atoms; and which may have a pyridyl group on the alkyl group, of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, such as 1-phenyl-1-(2,3, or 4-)pyridylmethyl, 1,1-diphenylmethyl, 1,1-di(4-fluorophenyl)methyl, 1-phenyl-1-(4-methoxyphenyl)methyl, 3,4-methylenedioxybenzyl, 3,4-ethylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2,5-difluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 3,5-difluorobenzyl, 2,6-difluorobenzyl, 3-trifluoromethylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 3,4-dimethoxybenzyl, 3,5-dimethoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 3,4-dimethylbenzyl, 2,3-dimethylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-cyanobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-methoxybenzyl, 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 2,5-dichlorobenzyl, 3,4-dichlorobenzyl, 2,6-dichlorobenzyl, 4-fluorobenzyl, 3-fluorobenzyl, 2-fluorobenzyl, 4-nitrobenzyl, 3-nitrobenzyl, 2-nitrobenzyl, 3-trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2-trifluoromethoxybenzyl, 4-methoxycarbonylbenzyl, 3-methoxycarbonylbenzyl, 4-tert-butylbenzyl, 4-ethylbenzyl, 4-isopropylbenzyl, 4-methoxy-3-chlorobenzyl, 2-(4-methoxyphenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methylphenyl)ethyl, 4-phenylbenzyl, 3,3-diphenylpropyl, 3-methyl-4-nitrobenzyl, 4-(4-methoxyphenyl)butyl, 2-(4-methylphenyl)ethyl, 4-tert-butoxycarbonylbenzyl, 3-chloro-6-methoxybenzyl, 4-acetylaminobenzyl, 4-nitro-3-methylbenzyl, 4-hydroxybenzyl, 3-hydroxybenzyl, 2-hydroxybenzyl, 4-tert-butyrylbenzyl, 4-benzyloxybenzyl, 4-pivaloylbenzyl, 2-(4-acetylphenyl)ethyl, 1-(3-propionylphenyl)ethyl, 3-(2-butyrylphenyl)propyl, 4-(4-pentanoylphenyl)butyl, 5-(3-hexanoylphenyl)pentyl, 6-(2,4-diacetylphenyl)hexyl, 1,1-dimethyl-2-(2,4,6-triacetylphenyl)ethyl, 2-methyl-3-(3,4-diacetylphenyl)propyl, 2-(4-aminophenyl)ethyl, 1-(3-propionylaminophenyl)ethyl, 3-(2-butyrylaminophenyl)propyl, 4-(4-pentanoylamino)phenylbutyl, 5-(hexanoylaminophenyl)pentyl, 6-(N-acetyl-N-propionylaminophenyl)hexyl, 1,1-dimethyl-2-(3,4-diaminophenyl)ethyl, 2-methyl-3-(3,4,5-triacetylaminophenyl)propyl, 2-(2-ethoxycarbonylphenyl)ethyl, 1-(3-propoxycarbonylphenyl)ethyl, 3-(4-pentyloxycarbonylphenyl)propyl, 4-(3-hexyloxycarbonylphenyl)butyl, 5-(3,4-dimethoxycarbonylphenyl)pentyl, 6-(3,4,5-triethoxycarbonylphenyl)hexyl, 1,1-dimethyl-2-(4-butoxycarbonylphenyl)ethyl, 2-methyl-3-(4-methoxycarbonylphenyl)propyl, 2-(2-cyanophenyl)ethyl, 1-(3-cyanophenyl)ethyl, 3-(4-cyanophenyl)propyl, 4-(2-cyanophenyl)butyl, 5-(3-cyanophenyl)pentyl, 6-(4-cyanophenyl)hexyl, 1,1-dimethyl-2-(2,4-dicyanophenyl)ethyl, 2-methyl-3-(2,4,6-tricyanophenyl)propyl, 2-(2-nitrophenyl)ethyl, 1-(3-nitrophenyl)ethyl, 3-(4-nitrophenyl)propyl, 4-(2-nitrophenyl)butyl, 5-(3-nitrophenyl)pentyl, 6-(4-nitrophenyl)hexyl, 1,1-dimethyl-2-(2,4-dinitrophenyl)ethyl, 2-methyl-3-(2,4,6-trinitrophenyl)propyl, 2-(2-phenylphenyl)ethyl, 1-(3-phenylphenyl)ethyl, 3-(4-phenylphenyl)propyl, 4-(2-phenylphenyl)butyl, 5-(3-phenylphenyl)pentyl, 6-(4-phenylphenyl)hexyl, 1,1-dimethyl-2-(2,4-diphenylphenyl)ethyl, 2-methyl-3-(2,4,6-triphenylphenyl)propyl, 2-(2-fluorophenyl)ethyl, 1-(3-bromophenyl)ethyl, 3-(4-iodophenyl)propyl, 4-(2-bromophenyl)butyl, 5-(3-chlorophenyl)pentyl, 6-(4-bromophenyl)hexyl, 1,1-dimethyl-2-(2,4-dichlorophenyl)ethyl, 2-methyl-3-(2,4,6-trifluorophenyl)propyl, 2-(2-ethylphenyl)ethyl, 1-(3-propylphenyl)ethyl, 3-(4-butylphenyl)propyl, 4-(2-pentylphenyl)butyl, 5-(3-hexylphenyl)pentyl, 6-(4-trifluoromethylphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethyl)phenyl]propyl, 2-(2-ethoxyphenyl)ethyl, 1-(3-propoxyphenyl)ethyl, 3-(4-butoxyphenyl)propyl, 4-(2-pentyloxyphenyl)butyl, 5-(3-hexyloxyphenyl)pentyl, 6-(4-trifluoromethoxyphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethoxyphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethoxy)phenyl]propyl, 2-(2-benzyloxyphenyl)ethyl, 1-[3-(2-phenylethoxy)phenyl]ethyl, 3-[4-(3-phenylpropoxy)phenyl]propyl, 4-[2-(4-phenylbutoxy)phenyl]butyl, 5-[3-(5-phenylpentyloxy)phenyl]pentyl, 6-[4-(6-phenylhexyloxy)phenyl]hexyl, 1,1-dimethyl-2-(2,4-dibenzyloxyphenyl)ethyl, 2-methyl-3-(2,4,6-tribenzyloxyphenyl)propyl, 2-(2-hydroxyphenyl)ethyl, 1-(3-hydroxyphenyl)ethyl, 3-(4-hydroxyphenyl)propyl, 4-(2-hydroxyphenyl)butyl, 5-(3-hydroxyphenyl)pentyl, 6-(4-hydroxyphenyl)hexyl, 1,1-dimethyl-2-(2,4-dihydroxyphenyl)ethyl, 2-methyl-3-(2,4,6-trihydroxyphenyl)propyl, 2-(3,4-methylenedioxyphenyl)ethyl, 1-(2,3-ethylenedioxyphenyl)ethyl, 3-(3,4-trimethylenedioxyphenyl)propyl, 4-(3,4-tetramethylenedioxyphenyl)butyl, 5-(3,4-methylenedioxyphenyl)pentyl, 6-(3,4-ethylenedioxyphenyl)hexyl, 1,1-dimethyl-2-(3,4-methylenedioxy)ethyl, 2-methyl-3-(3,4-methylenedioxyphenyl)propyl groups.

Examples of the pyridyl lower alkyl group which may have, on the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent include, in addition to the above described pyridyl lower alkyl groups, pyridylalkyl groups which may have, on the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxy group and a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 hydroxy groups as substituents, and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [2-methyl-(3,4,5, or 6-)pyridyl]methyl, [2-methyl-3-hydroxy-5-hydroxymethyl-(4 or 6-)pyridyl]methyl, 2-[3-ethyl-(2,4,5, or 6-)pyridyl]ethyl, 1-[4-propyl-(2,3,5, or 6-)pyridyl]ethyl, 3-[2-butyl-(3,4,5, or 6-)pyridyl]propyl, 4-[3-pentyl-(2,4,5, or 6-)pyridyl]butyl, 1,1-dimethyl-2-[4-hexyl-(2,3,5, or 6-)pyridyl]ethyl, 5-[2,3-dimethyl-(4,5, or 6-)pyridyl]pentyl, 6-[2,4,6-trimethyl-(3 or 5-)pyridyl]hexyl, 1-[2-hydroxy-(2,3,5, or 6-)pyridyl]isopropyl, 2-methyl-3-[3-hydroxy-(2,4,5, or 6-)pyridyl]propyl, [2-hydroxy-(3,4,5, or 6-)pyridyl]methyl, 2-[3-hydroxy-(2,4,5, or 6-)pyridyl]ethyl, 1-[4-hydroxy-(2,3,5, or 6-)pyridyl]ethyl, 3-[2-hydroxy-(3,4,5, or 6-)pyridyl]propyl, 4-[3-hydroxy-(2,4,5, or 6-)pyridyl]butyl, 1,1-dimethyl-2-[4-hydroxy-(2,3,5, or 6-)pyridyl]ethyl, 5-[2,3-dihydroxy-(4,5, or 6-)pyridyl]pentyl, 6-[2,4,6-trihydroxy-(3 or 5-)pyridyl]hexyl, [2-hydroxymethyl-(3,4,5, or 6-)pyridyl]methyl, 2-[3-(2-hydroxyethyl)-(2,4,5, or 6-)pyridyl}ethyl, 1-[4-(3-hydroxypropyl)-(2,3,5, or 6-)pyridyl]ethyl, 3-[2-(4-hydroxybutyl)-(3,4,5, or 6-)pyridyl]propyl, 4-[3-(5-hydroxypentyl)-(2,4,5, or 6-)pyridyl]butyl, 1,1-dimethyl-2-[4-(6-hydroxyhexyl)-(2,3,5, or 6-)pyridyl]ethyl, 5-[2,3-di(hydroxymethyl)-(4,5, or 6-)pyridyl]pentyl, 6-[2,4,6-tri(hydroxymethyl)-(3 or 5-)pyridyl]hexyl, 1-[2-hydroxymethyl-(2,3,5, or 6-)pyridyl]isopropyl, 2-methyl-3-[3-(2,3-dihydroxypropyl)-(2,4,5, or 6-)pyridyl]propyl, [2-methyl-3-(2,2,4-trihydroxybutyl)-(4,5, or 6-)pyridyl]methyl, [2-methyl-5-hydroxymethyl-(3,4, or 6-)pyridyl]methyl groups.

Examples of the pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as substituents on the pyrrole ring include pyrrolylalkyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms on the pyrrole and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1,2, or 3-)pyrrolyl]methyl, 2-[(1,2, or 3-)pyrrolyl]ethyl, 1-[(1,2, or 3-)pyrrolyl]ethyl, 3-[(1,2, or 3-)pyrrolyl]propyl, 4-[(1,2, or 3-)pyrrolyl]butyl, 5-[(1,2, or 3-)pyrrolyl]pentyl, 6-[(1,2, or 3-)pyrrolyl]hexyl, 1,1-dimethyl-2-[(1,2, or 3-)pyrrolyl]ethyl, 2-methyl-3-[(1,2, or 3-)pyrrolyl]propyl, [1-methyl-(2 or 3-)pyrrolyl]methyl, 2-[2-ethyl-(1,3,4, or 5-)pyrrolyl]ethyl, 1-[3-propyl-(1, 2, 4, or 5-)pyrrolyl]ethyl, 3-[1-butyl-(2,3, or 4-)pyrrolyl]propyl, 4-[2-pentyl-(1,3,4, or 5-)pyrrolyl]butyl, 5-[3-hexyl-(1,2,4, or 5-)pyrrolyl]pentyl, 6-[1,2-dimethyl-(3,4, or 5-)pyrrolyl]hexyl, 1,1-dimethyl-2-[1,2,3-trimethyl-(4 or 5-)pyrrolyl]ethyl, 2-methyl-3-[1-ethyl-2-methyl-(3,4, or 5-)pyrrolyl]propyl groups.

Examples of the benzoxazolyl lower alkyl group include benzoxazolylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2,4,5,6, or 7-)benzoxazolyl]methyl, 2-[(2,4,5,6, or 7-)benzoxazolyl]ethyl, 1-[(2,4,5,6, or 7-)benzoxazolyl]ethyl, 3-[(2,4,5,6, or 7-)benzoxazolyl]propyl, 4-[(2,4,5,6, or 7-)benzoxazolyl]butyl, 5-[(2,4,5,6, or 7-)benzoxazolyl]pentyl, 6-[(2,4,5,6, or 7-)benzoxazolyl]hexyl, 1,1-dimethyl-2-[(2,4,5,6, or 7-)benzoxazolyl]ethyl, 2-methyl-3-[(2,4,5,6, or 7-)benzoxazolyl]propyl.

Examples of the benzothiazolyl lower alkyl group include benzothiazolylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2,4,5,6, or 7-)benzothiazolyl]methyl, 2-[(2,4,5,6, or 7-)benzothiazolyl]ethyl, 1-[(2,4,5,6, or 7-)benzothiazolyl]ethyl, 3-[(2,4,5,6, or 7-)benzothiazolyl]propyl, 4-[(2,4,5,6, or 7-)benzothiazolyl]butyl, 5-[(2,4,5,6, or 7-)benzothiazolyl]pentyl, 6-[(2,4,5,6, or 7-)benzothiazolyl]hexyl, 1,1-dimethyl-2-[(2,4,5,6, or 7-)benzothiazolyl]ethyl, 2-methyl-3-[(2,4,5,6, or 7-)benzothiazolyl]propyl.

Examples of the furyl lower alkyl group include furylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a [(2 or 3-)furyl]methyl group, 2-[(2 or 3-)furyl]ethyl group, 1-[(2 or 3-)furyl]ethyl group, 3-[(2 or 3-)furyl]propyl group, 4-[(2 or 3-)furyl]butyl group, 5-[(2 or 3-)furyl]pentyl group, 6-[(2 or 3-)furyl]hexyl group, 1,1-dimethyl-2-[(2 or 3-)furyl]ethyl group, and 2-methyl-3-[(2 or 3-)furyl]propyl group.

Examples of the thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinylalkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2,3,4, or 5-)thiazolidinylmethyl, 2-[(2,3,4, or 5-)thiazolidinyl]ethyl, 1-[(2,3,4, or 5-)thiazolidinyl]ethyl, 3-[(2,3,4, or 5-)thiazolidinyl]propyl, 4-[(2,3,4, or 5-)thiazolidinyl]butyl, 5-[(2,3,4, or 5-)thiazolidinyl]pentyl, 6-[(2,3,4, or 5-)thiazolidinyl]hexyl, 1,1-dimethyl-2-[(2,3,4, or 5-)thiazolidinyl]ethyl, 2-methyl-3-[(2,3,4, or 5-)thiazolidinyl]propyl, [2,4-dioxo-(3 or 5-)thiazolidinyl]methyl, 2-[2-oxo-(3,4, or 5-)thiazolidinyl]ethyl, 1-[4-oxo-(2,3, or 5-)thiazolidinyl]ethyl, 3-[2-oxo-(3,4, or 5-)thiazolidinyl]propyl, 4-[5-oxo-(2,3, or 4-) thiazolidinyl]butyl, 5-[2,5-dioxo-(3 or 4-)thiazolidinyl]pentyl, 6-[2,4,5-trioxo-3-thiazolidinyl]hexyl, 1-[4,5-dioxo-(2 or 3-)thiazolidinyl]ethyl, 2-[4,5-dioxo-(2- or 3-)thiazolidinyl]ethyl, 1,1-dimethyl-2-[2,4-dioxo-(3 or 5-)thiazolidinyl]ethyl, 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propyl groups.

Examples of the thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinylidenealkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2,4, or 5-)thiazolidinylidenemethyl, (2,4, or 5-)thiazolidinylideneethyl, (2,4, or 5-)thiazolidinylidenepropyl, (2,4, or 5-)thiazolidinylideneisopropyl, (2,4, or 5-)thiazolidinylidenebutyl, (2,4, or 5-)thiazolidinylidenepentyl, (2,4, or 5-)thiazolidinylidenehexyl, 4,5-dioxo-2-thiazolidinylidenemethyl, 2,5-dioxo-4-thiazolidinylidenemethyl, 2,4-dioxo-5-thiazolidinylidenemethyl, 4-oxo-(2 or 5-)thiazolidinylideneethyl, 5-oxo-(2 or 4-)thiazolidinylidenepropyl, 2-oxo-(4, or 5-)thiazolidinylidenebutyl groups.

Examples of the benzoyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group, an amino group which may have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group which may have a halogen atom, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group include benzoyl groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group; an amino group which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents; a halogen atom; a linear or branched alkoxy group having 1 to 6 carbon atoms; a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents; a thiazolidinylalkyl group which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms; a thiazolidinylidenealkyl group which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms; and a linear or branched alkylenedioxy group having 1 to 4 carbon atoms such as benzoyl, 4-cyanobenzoyl, 3,4-methylenedioxybenzoyl, 2-aminobenzoyl, 3-aminobenzoyl, 4-aminobenzoyl, 3,4-diaminobenzoyl, 2,4,6-triaminobenzoyl, 4-methoxybenzoyl, 4-trifluoromethylbenzoyl, 4-chlorobenzoyl, 3,4-difluorobenzoyl, 2-fluorobenzoyl, 3-bromobenzoyl, 4-iodobenzoyl, 3,4-dimethoxybenzoyl, 4-fluorobenzoyl, 3-cyanobenzoyl, 2-cyanobenzoyl, 2,3-dicyanobenzoyl, 3,4,5-tricyanobenzoyl, 4-methylbenzoyl, 4-(2,4-dioxothiazolidinylmethyl)benzoyl, 4-(2,4-dioxothiazolidinylidenemethyl)benzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 2-ethylbenzoyl, 3-ethylbenzoyl, 4-ethylbenzoyl, 4-isopropylbenzoyl, 3-butylbenzoyl, 4-pentylbenzoyl, 4-hexylbenzoyl, 3,4-dimethylbenzoyl, 3,4-diethylbenzoyl, 2,4-dimethylbenzoyl, 2,5-dimethylbenzoyl, 2,6-dimethylbenzoyl, 3,4,5-trimethylbenzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 2-ethoxybenzoyl, 3-ethoxybenzoyl, 4-ethoxybenzoyl, 4-isopropoxybenzoyl, 3-butoxybenzoyl, 4-pentyloxybenzoyl, 4-hexyloxybenzoyl, 3,4-diethoxybenzoyl, 2,4-dimethoxybenzoyl, 2,5-dimethoxybenzoyl, 2,6-dimethoxybenzoyl, 3,4,5-trimethoxybenzoyl, 2-trifluoromethylbenzoyl, 3-trifluoromethylbenzoyl, 4-trifluoromethylbenzoyl, 2-(bromomethyl)benzoyl, 3-(2-chloroethyl)benzoyl, 4-(2,3-dichloropropyl)benzoyl, 4-(4-fluorobutyl)benzoyl, 3-(5-chloropentyl)benzoyl, 4-(5-bromohexyl)benzoyl, 4-(5,6-dibromohexyl)benzoyl, 3,4-di(trifluoromethyl)benzoyl, 3,4-di(4,4,4-trichlorobutyl)benzoyl, 2,4-di(3-chloro-2-methylpropyl)benzoyl, 2,5-di(3-chloropropyl)benzoyl, 2,6-di(2,2,2-trifluoroethyl)benzoyl, 3,4,5-tri(trifluoromethyl)benzoyl, 4-(2,2,2-trichloroethyl)benzoyl, 2-methyl-4-trifluoromethylbenzoyl, 3-ethyl-4-trichloromethylbenzoyl, 2-methoxy-4-trifluoromethylbenzoyl, 3-ethyl-4-fluorobenzoyl, 3-ethoxy-4-trichloromethylbenzoyl, 2-methyl-3-trifluoromethyl-4-trifluoromethylbenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 2,3-dibromobenzoyl, 2,4-diiodobenzoyl, 2,5-difluorobenzoyl, 2,6-dichlorobenzoyl, 2,4,6-trichlorobenzoyl, 2,4-difluorobenzoyl, 3,4-difluorobenzoyl, 3,5-difluorobenzoyl, 2,6-difluorobenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 2,5-dichlorobenzoyl, 3,4-dichlorobenzoyl, 2,6-dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,4,6-trifluorobenzoyl, 2,4-difluorobenzoyl, 3,4-difluorobenzoyl, 3,4-methylenedioxybenzoyl, 3,4-trimethylenedioxybenzoyl, 2,3-ethylenedioxybenzoyl, 3,4-trimethylenedioxybenzoyl, 2,3-tetramethylenedioxybenzoyl, 2,3-methylenedioxybenzoyl, 3,4-ethylenedioxybenzoyl, 2-methanesulfonylaminobenzoyl groups.

Examples of the thiazolidinyl lower alkanoyl group which may be substituted on the thiazolidine ring with 1 to 3 groups selected from the group consisting of an oxo group and a group of the formula:


wherein Ra and Rb each represent a lower alkyl group, include thiazolidinylalkanoyl groups which may be substituted on the thiazolidine ring with 1 to 3 substituents selected from the group consisting of an oxo group and a group of the formula:


wherein Ra and Rb each represent a linear or branched alkyl group having 1 to 6 carbon atoms, and of which the alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-[(2,3,4, or 5-)thiazolidinyl]acetyl, 3-[(2,3,4, or 5-)thiazolidinyl]propionyl, 2-[(2,3,4, or 5-)thiazolidinyl]propionyl, 4-[(2,3,4, or 5-)thiazolidinyl]butyryl, 5-[(2,3,4, or 5-)thiazolidinyl]pentanoyl, 6-[(2,3,4, or 5-)thiazolidinyl]hexanoyl, 2,2-dimethyl-3-[(2,3,4, or 5-)thiazolidinyl]propionyl, 2-methyl-3-[(2,3,4, or 5-)thiazolidinyl]propionyl, [2,4-dioxo-(3 or 5-)thiazolidinyl]acetyl, 3-[2-oxo-(3,4, or 5-)thiazolidinyl]propionyl, 2-[4-oxo-(2,3, or 5-)thiazolidinyl]propionyl, 4-[5-oxo-(2,3, or 4-)thiazolidinyl]butyryl, 5-[2,5-dioxo-(3 or 4-)thiazolidinyl]pentanoyl, 6-[2,4,5-trioxo-3-thiazolidinyl]hexanoyl, 2-[4,5-dioxo-(2 or 3-)thiazolidinyl]acetyl, 2,2-dimethyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl, 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl, 2-[4-oxo-2-isopropylidenehydrazono-(3 or 5-)thiazolidinyl]acetyl, 2-[2-oxo-5-isopropylidenehydrazono-(3 or 4-)thiazolidinyl]acetyl, 2-[2,4-di(isopropylidenehydrazono)-(3 or 5-)thiazolidinyl]acetyl, 3-[2-methylidenehydrazono-(3,4, or 5-)thiazolidinyl]propionyl, 2-[4-ethylidenehydrazono-(2,3, or 5-)thiazolidinyl]-propionyl, 4-[5-propylidenehydrazono-(2,3, or 4-)thiazolidinyl]butyryl, 5-[2,5-di(isopropylidenehydrazono)-(3 or 4-)thiazolidinyl]pentanoyl, 6-[2,4,5-tri(isopropylidenehydrazono)-3-thiazolidinyl]-hexanoyl, 2-[4,5-di(isopropylidenehydrazono)-(2 or 3-)thiazolidinyl]acetyl, 2,2-dimethyl-3-[4-butylidenehydrazono-(2,3, or 5-)thiazolidinyl]-propionyl, 2-methyl-3-[5-pentylidene-(2,3, or 4-)thiazolidinyl]propionyl, 2-(hexylidenehydrazono)-(3,4, or 5-)thiazolidinylacetyl groups.

Examples of the lower alkyl group which may have a substituent selected from the group consisting of a hydroxyl group and a halogen atom include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 substituents selected from the group consisting of a hydroxy group and a halogen atom such as hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dibromohexyl, 2-hydroxy-3-fluoropropyl, 2,2-dichloro-3-hydroxybutyl groups.

Examples of the phenyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a benzoyl group which may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group which may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group include phenyl groups which may be substituted on the phenyl group with 1 to 3 groups selected from the group consisting of a carbamoyl group which may have 1 or 2 groups selected from the group consisting of an alkoxyalkyl group of the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a carboxy group, a cyano group, a phenyl group, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a benzoyl group which may have 1 to 3 halogen atoms as substituents on the phenyl ring, a phenylalkyl group which may have 1 to 3 halogen atoms as substituents on the phenyl ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, and a hydroxyl group such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,3-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-(bromomethoxy)phenyl, 3-(2-chloroethoxy)phenyl, 4-(2,3-dichloropropoxy)phenyl, 4-(4-fluorobutoxy)phenyl, 3-(5-chloropentyloxy)phenyl, 4-(5-bromohexyloxy)phenyl, 4-(5,6-dibromohexyloxy)phenyl, 3,4-di(trifluoromethoxy)phenyl, 3,4-di(4,4,4-trichlorobutoxy)phenyl, 2,4-di(3-chloro-2-methoxypropyl)phenyl, 2,5-di(3-chloropropoxy)phenyl, 2,6-di(2,2,2-trifluoroethoxy)phenyl, 3,4,5-tri(trifluoromethoxy)phenyl, 4-(2,2,2-trichloroethoxy)phenyl, 2-methyl-4-trifluoromethoxyphenyl, 3-ethyl-4-trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, 3-ethyl-4-trichloromethylphenyl, 2-methoxycarbonylphenyl, 3-methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 2-ethoxycarbonylphenyl, 3-ethoxycarbonylphenyl, 4-ethoxycarbonylphenyl, 4-isopropoxycarbonylphenyl, 3-butoxycarbonylphenyl, 4-tert-butoxycarbonylphenyl, 4-pentyloxycarbonylphenyl, 4-hexyloxycarbonylphenyl, 3,4-dimethoxycarbonylphenyl, 3,4-diethoxycarbonylphenyl, 2,4-dimethoxycarbonylphenyl, 2,5-diethoxycarbonylphenyl, 2,6-dimethoxycarbonylphenyl, 3,4,5-triethoxycarbonylphenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 3,4-dicyanophenyl, 3,5-dicyanophenyl, 2,4-dicyanophenyl, 2,5-dicyanophenyl, 2,6-dicyanophenyl, 3,4,5-tricyanophenyl, 2-phenylphenyl, 3-phenylphenyl, 4-phenylphenyl, 3,4-diphenylphenyl, 3,5-diphenylphenyl, 2,4-diphenylphenyl, 2,5-diphenylphenyl, 2,6-diphenylphenyl, 3,4,5-triphenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,4,6-trichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,5-difluorophenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,4,6-trifluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2,3-dibromophenyl, 2,4-diiodophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 3,4-dihydroxyphenyl, 3,5-dihydroxyphenyl, 2,4-dihydroxyphenyl, 2,5-dihydroxyphenyl, 2,6-dihydroxyphenyl, 3,4,5-trihydroxyphenyl, 3-benzylphenyl, 2-(2-phenylethyl)phenyl, 4-(1-phenylethyl)phenyl, 2-(3-phenylpropyl)phenyl, 3-(4-phenylbutyl)phenyl, 4-(5-phenylpentyl)phenyl, 2-(6-phenylhexyl)phenyl, 4-(1,1-dimethyl-2-phenylethyl)phenyl, 3-(2-methyl-3-phenylpropyl)phenyl, 2-(4-fluorobenzyl)phenyl, 2-methyl-5-chlorophenyl, 2-methoxy-5-chlorophenyl, 4-(4-fluorobenzoyl)phenyl, 4-(4-fluorobenzyl)phenyl, 3-(2-chlorobenzyl)phenyl, 4-(3-chlorobenzyl)phenyl, 2-(4-chlorobenzyl)phenyl, 3-[2-(4-fluorophenyl)ethyl]phenyl, 4-[2-(4-chlorophenyl)ethyl]phenyl, 2-(3,4-dibromobenzyl)phenyl, 3-(3,4-diiodobenzyl)phenyl, 4-(2,4-difluorobenzyl)phenyl, 2-(2,5-dichlorobenzyl)-phenyl, 3-(2,6-dichlorobenzyl)phenyl, 4-(3,4,5-trifluorobenzyl)phenyl, 2-[3-(4-chlorophenyl)propyl]phenyl, 3-[1-(2-bromophenyl)ethyl]phenyl, 4-[4-(3-fluorophenyl)butyl]phenyl, 2-[5-(4-iodophenyl)pentyl]phenyl, 3-[6-(4-chlorophenyl)hexyl]phenyl, 2-[1,1-dimethyl-2-(3-fluorophenyl)ethyl]phenyl, 4-[2-methyl-3-(4-chlorophenyl)propyl]phenyl, 2,4-dibenzylphenyl, 2,4,6-tribenzylphenyl, 2-chloro-4-cyanophenyl, 3-hydroxy-4-phenylphenyl, 3-ethoxycarbonyl-2-benzoylphenyl, 2-benzyl-4-methyl-6-methoxyphenyl, 4-[(2-methoxyethyl)carbamoyl]phenyl, 3-(N-ethyl-N-isopropylcarbamoyl)phenyl, 4-dimethylcarbamoylphenyl, 2-carboxyphenyl, 3-carboxyphenyl, 4-carboxyphenyl, groups.

Examples of the phenyl group which has a lower alkylenedioxy group as a substituent on the phenyl ring include phenyl groups which has a linear or branched alkylenedioxy group having 1 to 4 carbon atom as a substituent on the phenyl ring such as a 3,4-methylenedioxyphenyl group, 3,4-trimethylenedioxyphenyl group, 2,3-ethylenedioxyphenyl group, 2,3-tetramethylenedioxyphenyl group, 2,3-methylenedioxyphenyl group, 3,4-ethylenedioxyphenyl group, and 2,3-trimethylenedioxyphenyl group.

Examples of the naphthyl lower alkyl group include naphthylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a (1 or 2-)naphthylmethyl group, 2-[(1 or 2-)naphthyl]ethyl group, 1-[(1 or 2-)naphthyl]ethyl group, 3-[(l or 2-)naphthyl]propyl group, 4-[(l or 2-)naphthyl]butyl group, 5-[(1 or 2-)naphthyl]pentyl group, 6-[(1 or 2-)naphthyl]hexyl group, 1,1-dimethyl-2-[(1 or 2-)naphthyl]ethyl group, and 2-methyl-3-[(1 or 2-)naphthyl]propyl group.

Examples of the phenoxy group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent include phenoxy groups which may be substituted on the phenyl group with 1 to 3 groups selected from the group consisting of a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as phenoxy, 2-methylphenoxy, 3-methylphenyl, 4-methylphenoxy, 2-ethylphenoxy, 3-ethylphenoxy, 4-ethylphenoxy, 4-isopropylphenoxy, 3-butylphenoxy, 4-pentylphenoxy, 4-hexylphenoxy, 3,4-dimethylphenoxy, 3,4-diethylphenoxy, 2,4-dimethylphenoxy, 2,5-dimethylphenoxy, 2,6-dimethylphenoxy, 3,4,5-trimethylphenoxy, 2-methoxyphenoxy, 3-methoxyphenoxy, 4-methoxyphenoxy, 2-ethoxyphenoxy, 3-ethoxyphenoxy, 4-ethoxyphenoxy, 4-isopropoxyphenoxy, 3-butoxyphenoxy, 4-pentyloxyphenoxy, 4-hexyloxyphenoxy, 3,4-dimethoxyphenoxy, 3,4-diethoxyphenoxy, 2,4-dimethoxyphenoxy, 2,5-dimethoxyphenoxy, 2,6-dimethoxyphenoxy, 3,4,5-trimethoxyphenoxy, 2-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, 2-(bromomethoxy)phenoxy, 3-(2-chloroethoxy)phenoxy, 4-(2,3-dichloropropoxy)phenoxy, 4-(4-fluorobutoxy)phenoxy, 3-(5-chloropentyloxy)phenoxy, 4-(5-bromohexyloxy)phenoxy, 4-(5,6-dibromohexyloxy)phenoxy, 3,4-di(trifluoromethoxy)phenoxy, 3,4-di(4,4,4-trichlorobutoxy)phenoxy, 2,4-di(3-chloro-2-methoxypropyl)phenoxy, 2,5-di(3-chloropropoxy)phenoxy, 2,6-di(2,2,2-trifluoroethoxy)phenoxy, 3,4,5-tri(trifluoromethoxy)phenoxy, 4-(2,2,2-trichloroethoxy)phenoxy, 2-methyl-4-trifluoromethoxyphenoxy, 3-ethyl-4-trichloromethoxyphenoxy, 2-methoxy-4-trifluoromethoxyphenoxy, 3-ethoxy-4-trichloromethoxyphenoxy, 2-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 4-trifluoromethylphenoxy, 2-(bromomethyl)phenoxy, 3-(2-chloroethyl)phenoxy, 4-(2,3-dichloropropyl)phenoxy, 4-(4-fluorobutyl)phenoxy, 3-(5-chloropentyl)phenoxy, 4-(5-bromohexyl)phenoxy, 4-(5,6-dibromohexyl)phenoxy, 3,4-di(trifluoromethyl)phenoxy, 3,4-di(4,4,4-trichlorobutyl)phenoxy, 2,4-di(3-chloro-2-methylpropyl)phenoxy, 2,5-di(3-chloropropyl)phenoxy, 2,6-di(2,2,2-trifluoroethyl)phenoxy, 3,4,5-tri(trifluoromethyl)phenoxy, 4-(2,2,2-trichloroethyl)phenoxy, 2-methyl-4-trifluoromethylphenoxy, 3-ethyl-4-trichloromethylphenoxy, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 3,5-dicyanophenoxy, 3,4-dicyanophenoxy, 2,3-dicyanophenoxy, 2,4-dicyanophenoxy, 2,5-dicyanophenoxy, 2,6-dicyanophenoxy, 3,4,5-tricyanophenoxy, 2-cyano-4-methylphenoxy, 3-cyano-4-methoxyphenoxy, 3-cyano-5-trifluoromethylphenoxy, 4-cyano-3-trifluoromethoxyphenoxy groups.

Examples of the phenyl lower alkoxy group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkyloxy group which may have a halogen atom as a substituent include, in addition to the above described phenyl lower alkoxy groups, phenylalkoxy groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and of which the alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms such as 2,5-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 3,5-difluorobenzyloxy, 2,6-difluorobenzyloxy, 3-trifluoromethylbenzyloxy, 2-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 3,4-dimethoxybenzyloxy, 3,5-dimethoxybenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-methylbenzyloxy, 3-methylbenzyloxy, 4-methylbenzyloxy, 3,4-dimethylbenzyloxy, 2,3-dimethylbenzyloxy, 2-methoxybenzyloxy, 3-methoxybenzyloxy, 4-methoxybenzyloxy, 2,3-dichlorobenzyloxy, 2,4-dichlorobenzyloxy, 2,5-dichlorobenzyloxy, 3,4-dichlorobenzyloxy, 2,6-dichlorobenzyloxy, 4-fluorobenzyloxy, 3-fluorobenzyloxy, 2-fluorobenzyloxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 2-trifluoromethoxybenzyloxy, 4-tert-butylbenzyloxy, 4-ethylbenzyloxy, 4-isopropylbenzyloxy, 4-methoxy-3-chlorobenzyloxy, 2-(4-methoxyphenyl)ethoxy, 2-(4-fluorophenyl)ethoxy, 2-(4-chlorophenyl)ethoxy, 2-(3-methoxyphenyl)ethoxy, 2-(4-methylphenyl)ethoxy, 3-methyl-4-chlorobenzyloxy, 4-(4-methoxyphenyl)butoxy, 2-(4-methylphenyl)ethoxy, 4-tert-butoxybenzyloxy, 3-chloro-6-methoxybenzyloxy, 4-methoxy-3-methylbenzyloxy, 2-(2-fluorophenyl)ethoxy, 1-(3-bromophenyl)ethoxy, 3-(4-iodophenyl)propoxy, 4-(2-bromophenyl)butoxy, 5-(3-chlorophenyl)pentyloxy, 6-(4-bromophenyl)hexyloxy, 1,1-dimethyl-2-(2,4-dichlorophenyl)ethoxy, 2-methyl-3-(2,4,6-trifluorophenyl)propoxy, 2-(2-ethylphenyl)ethoxy, 1-(3-propylphenyl)ethoxy, 3-(4-butylphenyl)propoxy, 4-(2-pentylphenyl)butoxy, 5-(3-hexylphenyl)pentyloxy, 6-(4-trifluoromethylphenyl)hexyloxy, 1,1-dimethyl-2-(2,4-dimethylphenyl)ethoxy, 2-methyl-3-[2,4,6-tri(trifluoromethyl)phenyl]propoxy, 2-(2-ethoxyphenyl)ethoxy, 1-(3-propoxyphenyl)ethoxy, 3-(4-butoxyphenyl)propoxy, 4-(2-pentyloxyphenyl)butoxy, 5-(3-hexyloxyphenyl)pentyloxy, 6-(4-trifluoromethoxyphenyl)hexyloxy, 1,1-dimethyl-2-(2,4-dimethoxyphenyl)ethoxy, 2-methyl-3-[2,4,6-tri(trifluoromethoxy)phenyl]propoxy groups.

Examples of the 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring include 1,2,3,4-tetrahydronaphthyl substituted alkyl groups which may have 1 to 5 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the 1,2,3,4-tetrahydronaphthalene ring, and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1,2,5, or 6-)1,2,3,4-tetrahydronaphthylmethyl, 2-[(1,2,5, or 6-)1,2,3,4-tetrahydronaphthyl]ethyl, 1-[(1,2,5, or 6-)1,2,3,4-tetrahydronaphthyl]ethyl, 3-[(1,2,5, or 6-)1,2,3,4-tetrahydronaphthyl]propyl, 4-[(1,2,5, or 6-)1,2,3,4-tetrahydronaphthyl]butyl, 5-[(1,2,5, or 6-)1,2,3,4-tetrahydronaphthyl]pentyl, 6-[(1,2,5, or 6-)1,2,3,4-tetrahydronaphthyl]hexyl, 1,1-dimethyl-2-[(1,2,5, or 6-)1,2,3,4-tetrahydronaphthyl]ethyl, 2-methyl-3-[(1,2,5, or 6-)1,2,3,4-tetrahydronaphthyl]propyl, 1,1,4,4-tetramethyl(2,3,5, or 6-)1,2,3,4-tetrahydronaphthylmethyl, 1,1,4,4,5-pentamethyl(2,3,6,7, or 8-)1,2,3,4-tetrahydronaphthylmethyl, 1,4,4-trimethyl(2,3,5,6,7, or 8-)1,2,3,4-tetrahydronaphthylmethyl, 5,6-dimethyl(2, 3, 7, or 8-)1,2,3,4-tetrahydronaphthylmethyl, 2-[1-methyl-(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydronaphthyl]ethyl, 1-[2-ethyl-(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydronaphthyl]ethyl, 3-[3-propyl-(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydronaphthyl]propyl, 4-[(4-butyl-1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydronaphthyl]butyl, 5-[5-pentyl-(1,2,3,4,6,7, or 8-)1,2,3,4-tetrahydronaphthyl]pentyl, 6-[6-hexyl-(1,2,3,4,5,7, or 8-)1,2,3,4-tetrahydronaphthyl]hexyl, 1,1-dimethyl-2-[1,7-dimethyl-(1,2,3,4,5,6, or 8-)1,2,3,4-tetrahydronaphthyl]ethyl, 2-methyl-3-[1,1,4-trimethyl-(2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydronaphthyl]propyl groups.

Examples of the piperidinyl group which may have 1 to 3 lower alkyl groups as substituents on the piperidine ring include piperidinyl group which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperidine ring such as (1,2,3, or 4-)piperidinyl, 1-methyl-(2,3, or 4-)piperidinyl, 1-ethyl-(2,3, or 4-)piperidinyl, 1-propyl-(2,3, or 4-)piperidinyl, 1-isopropyl-(2,3, or 4-)piperidinyl, 1-butyl-(2,3, or 4-)piperidinyl, 1-isobutyl-(2,3, or 4-)piperidinyl, 1-tert-butyl-(2,3, or 4-)piperidinyl, 1-pentyl-(2,3, or 4-)piperidinyl, 1-hexyl-(2,3, or 4-)piperidinyl, 1,2-dimethyl-(3,4,5, or 6-)piperidinyl, 1,2,6-trimethyl-(3,4, or 5-)piperidinyl groups.

Examples of the quinolyl lower alkyl group include quinolylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a (2,3,4,5,6,7 or 8-)quinolyl-methyl group, 2-[(2,3,4,5,6,7 or 8-)quinolyl]ethyl group, 1-[(2,3,4,5,6,7 or 8-)quinolyl]ethyl group, 3-[(2,3,4,5,6,7 or 8-)quinolyl]propyl group, 4-[(2,3,4,5,6,7 or 8-)quinolyl]butyl group, 5-[(2,3,4,5,6,7 or 8-)quinolyl]pentyl group, and 6-[(2,3,4,5,6,7 or 8-)quinolyl]hexyl group.

Examples of the 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group include 1,2,3,4-tetrazolylalkyl groups which may have, on the tetrazole ring, a substituent selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, the 1,2,3,4-tetrazolylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, such as [(1 or 0.5-)1,2,3,4-tetrazolyl]methyl, 2-[(1 or 5-)1,2,3,4-tetrazolyl]ethyl, 1-[(1 or 5-)1,2,3,4-tetrazolyl]ethyl, 3-[(1 or 5-)1,2,3,4-tetrazolyl]propyl, 4-[(1 or 5-)1,2,3,4-tetrazolyl]butyl, 5-[(1 or 5-)1,2,3,4,-tetrazolyl]pentyl, 6-[(1 or 5-)1,2,3,4-tetrazolyl]hexyl, 5-[1-methyl-5-(1,2,3,4-tetrazolyl)]pentyl, 6-[1-methyl-5-(1,2,3,4-tetrazolyl)]hexyl, 5-methyl-1-(1,2,3,4-tetrazolyl)methyl, 2-[5-ethyl-1-(1,2,3,4-tetrazolyl]hexyl, 1,1-dimethyl-2-[(1 or 5-)1,2,3,4-tetrazolyl)]ethyl, 2-methyl-3-[(1 or 5-)1,2,3,4-tetrazolyl]propyl, [1-methyl-5-(1,2,3,4-tetrazolyl)]methyl, [1-ethyl-5-(1,2,3,4-tetrazolyl)]methyl, 2-[1-propyl-5-(1,2,3,4-tetrazolyl)]ethyl, 1-[1-butyl-5-(1,2,3,4-tetrazolyl)]ethyl, 3-[1-pentyl-5-(1,2,3,4-tetrazolyl)]propyl, 3-[5-propyl-1-(1,2,3,4-tetrazolyl)]propyl, 4-[5-butyl-1-(1,2,3,4-tetrazolyl)]butyl, 5-[5-pentyl-1-(1,2,3,4-tetrazolyl)]pentyl, 6-[5-hexyl-1-(1,2,3,4-tetrazolyl)]hexyl, [1-ethyl-5-(1,2,3,4-tetrazolyl)]methyl, [1-benzyl-5-(1,2,3,4-tetrazolyl)]methyl, 1-[(2-phenylethyl)-5-(1,2,3,4-tetrazolyl)]methyl, 2-[1-(3-phenylpropyl)-5-(1,2,3,4-tetrazolyl)]ethyl, 1-[l-(4-phenylbutyl)-5-(1,2,3,4-tetrazolyl)]ethyl, 3-[1-(5-phenylpentyl)-5-(1,2,3,4-tetrazolyl)]propyl, 4-[l-(6-phenylhexyl)-5-(1,2,3,4-tetrazolyl)]butyl, 5-[1-(1,1-dimethyl-2-phenylethyl)-5-(1,2,3,4-tetrazolyl)]methyl, 6-[1-(2-methyl-3-phenylpropyl)-5-(1,2,3,4-tetrazolyl)]hexyl, 5-benzyl-1-(1,2,3,4-tetrazolyl)methyl, 2-[5-(1-phenylethyl)-1-(1,2,3,4-tetrazolyl)]ethyl, 3-[5-(3-phenylpropyl)-1-(1,2,3,4-tetrazolyl)]propyl, 4-[5-(4-phenylbutyl)-1-(1,2,3,4-tetrazolyl)]butyl, 5-[5-(5-phenylpentyl)-1-(1,2,3,4-tetrazolyl)]pentyl, 6-[5-(6-phenylhexyl)-1-(1,2,3,4-tetrazolyl)]hexyl groups.

Examples of the thiazolyl lower alkyl group which may have a phenyl group as a substituent on the thiazole ring include thiazolylalkyl groups which may have 1 or 2 phenyl groups as substituents on the thiazole ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2,4, or 5-)thiazolyl]methyl, 2-[(2,4, or 5-)thiazolyl]ethyl, 1-[(2,4, or 5-)thiazolyl]ethyl, 3-[(2,4, or 5-)thiazolyl]propyl, 4-[(2,4, or 5-)thiazolyl]butyl, 5-[(2,4, or 5-)thiazolyl]pentyl, 6-[(2,4, or 5-)thiazolyl]hexyl, 1,1-dimethyl-2-[(2,4, or 5-)thiazolyl]ethyl, 2-methyl-3-[(2,4, or 5-)thiazolyl]propyl, [2-phenyl-(4 or 5-)thiazolyl]-methyl, 2-[4-phenyl-(2 or 5-)thiazolyl]ethyl, 1-[5-phenyl-(2 or 4-)thiazolyl]ethyl, 3-[2-phenyl-(2 or 5-)thiazolyl]propyl, 4-(2,4-diphenyl-5-thiazolyl)butyl, 5-(2,5-diphenyl-4-thiazolyl)pentyl, 6-(4,5-diphenyl-2-thiazolyl)hexyl, 1,1-dimethyl-2-[2-phenyl-(4 or 5-)thiazolyl]ethyl, 2-methyl-3-[4-phenyl-(2 or 5-)thiazolyl]propyl, [4-phenyl-(2 or 5-)thiazolyl]-methyl, [5-phenyl-(2 or 4-)thiazolyl]methyl, (2,4-diphenyl-5-thiazolyl)methyl, (2,5-diphenyl-4-thiazolyl)methyl, (4,5-diphenyl-2-thiazolyl)methyl groups.

Examples of the benzoyl lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom include benzoylalkyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms and a halogen atom such as benzoylmethyl, 2-benzoylethyl, 1-benzoylethyl, 3-benzoylpropyl, 4-benzoylbutyl, 5-benzoylpentyl, 6-benzoylhexyl, 1,1-dimethyl-2-benzoylethyl, 2-methyl-3-benzoylpropyl, 4-fluorobenzoylmethyl, 2-chlorobenzoylmethyl, 3-chlorobenzoylmethyl, 4-chlorobenzoylmethyl, 2-(4-fluorobenzoyl)ethyl, 2-(4-chlorobenzoyl)ethyl, 3,4-dibromobenzoylmethyl, 3,4-diiodobenzoylmethyl, 2,4-difluorobenzoylmethyl, 2,5-dichlorobenzoylmethyl, 2,6-dichlorobenzoylmethyl, 3,4,5-trifluorobenzoylmethyl, 3-(4-chlorobenzoyl)propyl, 1-(2-bromobenzoyl)ethyl, 4-(3-fluorobenzoyl)butyl, 5-(4-iodobenzoyl)pentyl, 6-(4-chlorobenzoyl)hexyl, 1,1-dimethyl-2-(3-fluorobenzoyl)ethyl, 2-methyl-3-(4-chlorobenzoyl)propyl, 2-methoxybenzoylmethyl, 2-(3-methoxybenzoyl)ethyl, 2-(4-methoxybenzoyl)ethyl, 4-methoxybenzoylmethyl, 1-(2-ethoxybenzoyl)ethyl, 3-(3-ethoxybenzoyl)propyl, 4-(4-ethoxybenzoyl)butyl, 5-(4-isopropoxybenzoyl)pentyl, 6-(3-butoxybenzoyl)hexyl, 1,1-dimethyl-2-(4-pentyloxybenzoyl)ethyl, 2-methyl-3-(4-hexyloxybenzoyl)propyl, 3,4-dimethoxybenzoylmethyl, 3,4-diethoxybenzoylmethyl, 2,4-dimethoxybenzoylmethyl, 2,5-dimethoxybenzoylmethyl, 2,6-dimethoxybenzoylmethyl, 3,4,5-trimethoxybenzoylmethyl, 2-chloro-4-methoxybenzoylmethyl, 3-fluoro-5-ethoxybenzoylmethyl groups.

Examples of the piperidinyl lower alkyl group which may have a lower alkyl group as a substituent on the piperidine ring include piperidinylalkyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms on the piperidine ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1,2,3, or 4-)piperidinyl]methyl, 2-[(1,2,3, or 4-)piperidinyl]-ethyl, 1-[(1,2,3, or 4-)piperidinyl]ethyl, 3-[(1,2,3, or 4-)piperidinyl]propyl, 4-[(1,2,3, or 4-)piperidinyl]butyl, 5-[(1,2,3, or 4-)piperidinyl]pentyl, 6-[(1,2,3, or 4-)piperidinyl]hexyl, 1,1-dimethyl-2-[(1,2,3, or 4-)piperidinyl]ethyl, 2-methyl-3-[(1,2,3, or 4-)piperidinyl]propyl, [1-methyl-(2,3, or 4-)piperidinyl]methyl, 2-[1-ethyl-(2,3, or 4-)piperidinyl]ethyl, 1-[4-propyl-(1,2, or 3-)piperidinyl]ethyl, 3-[3-isopropyl-(1,2,4,5, or 6-)piperidinyl]propyl, 4-[2-butyl-(1,3,4,5, or 6-)piperidinyl]butyl, 5-[l-isobutyl-(2,3, or 4-)piperidinyl]pentyl, 6-[1-tert-butyl-(2,3, or 4-)piperidinyl]hexyl, 1,1-dimethyl-2-[4-pentyl-(1,2, or 3-)piperidinyl]ethyl, 2-methyl-3-[l-hexyl-(2,3, or 4-)piperidinyl]propyl, [1,2-dimethyl-(3,4,5, or 6-)piperidinyl]methyl, [1,2,6-trimethyl-(3,4, or 5-)piperidinyl]methyl groups.

Examples of the imidazolyl group which may have 1 to 3 phenyl groups as substituents on the imidazole ring include imidazolyl groups which may have 1 to 3 phenyl groups as substituents on the imidazole ring such as a (1,2,4 or 5-)imidazolyl group, 1-phenyl-(2,4 or 5-)imidazolyl group, 2-phenyl-(1,4 or 5-)imidazolyl group, 4-phenyl-(1,2 or 5-)imidazolyl group, 5-phenyl-(1,2 or 4-)imidazolyl group, 1,2-diphenyl-(4 or 5-)imidazolyl group, 2,4-diphenyl-(l or 5-)imidazolyl group, 4,5-diphenyl-(1 or 2-)imidazolyl group, 2,5-diphenyl-(1 or 4-)imidazolyl group, and 2,4,5-triphenyl-1-imidazolyl group.

Examples of the benzimidazolyl group which may have 1 to 3 lower alkyl groups as substituents on the benzimidazole ring include benzimidazolyl group which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the benzimidazole ring such as (1,2,4,5,6, or 7-)benzimidazolyl, 1-methyl-(2,4,5,6, or 7-)benzimidazolyl, 2-ethyl-(1,4,5,6, or 7-)benzimidazolyl, 4-propyl-(1,2,5,6, or 7-)benzimidazolyl, 5-butyl-(1,2,4,6, or 7-)benzimidazolyl, 6-pentyl-(1,2,4,5, or 7-)benzimidazolyl, 7-hexyl-(1,2,4,5, or 6-)benzimidazolyl, 1-ethyl-(2,4,5,6, or 7-)benzimidazolyl]hexyl, 1-butyl-(2,4,5,6, or 7-)benzimidazolyl, 1-isopropyl-(1,2,4,5,6, or 7-)benzimidazolyl, 1,2-dimethyl-(4,5,6, or 7-)benzimidazolyl, 1-methyl-4-ethyl-(2,5,6, or 7-)benzimidazolyl, 1-propyl-5-methyl-(2,4,6, or 7-)benzimidazolyl, 1,2,5-trimethyl-(2,4,5,6, or 7-)benzimidazolyl groups.

Examples of the pyridyl lower alkoxy group include pyridylalkoxy group of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a (2,3 or 4-)pyridylmethoxy group, 2-[(2,3 or 4-)pyridyl]ethoxy group, 1-[(2,3 or 4-)pyridyl]ethoxy group, 3-[(2,3 or 4-)pyridyl]propoxy group, 4-[(2,3 or 4-)pyridyl]butoxy group, 1-1-dimethyl-2-[(2,3 or 4-)pyridyl]ethoxy group, 5-[(2,3 or 4-)pyridyl]pentyloxy group, 6-[(2,3 or 4-)pyridyl]hexyloxy group, 1-[(2,3 or 4-)pyridyl]isopropoxy group, and 2-methyl-3-[(2,3 or 4-)pyridyl]propoxy group.

Examples of the 1,2,3,4-tetrahydroquinolyl lower alkyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring include 1,2,3,4-tetrahydroquinolylalkyl groups which may have 1 or 2 oxo groups as substituents on the tetrahydroquinoline ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolylmethyl, 2-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 1-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 3-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]propyl, 4-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]butyl, 5-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]pentyl, 6-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]hexyl, 1,1-dimethyl-2-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 2-methyl-3-[(1,2,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]propyl, [2-oxo-(1,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]methyl, [4-oxo-(1,2,3,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]methyl, [2,4-dioxo-(1,3,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]methyl, 2-[2-oxo-(1,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 3-[4-oxo-(1,2,3,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]propyl, 4-[2,4-dioxo-(1,3,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]butyl, 5-[2-oxo-(1,3,4,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]pentyl, 6-[4-oxo-(1,2,3,5,6,7, or 8-)1,2,3,4-tetrahydroquinolyl]hexyl groups.

Examples of the 1,3,4-oxadiazolyl lower alkyl group which may have an oxo group as a substituent on the oxadiazole ring include 1,3,4-oxadiazolylalkyl groups which may have an oxo group as a substituent on the oxadiazole ring and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2 or 5-)1,3,4-oxadiazolylmethyl, 2-[(2 or 5-)1,3,4-oxadiazolyl]ethyl, 1-[(2 or 5-)1,3,4-oxadiazolyl]ethyl, 3-[(2 or 5-)1,3,4-oxadiazolyl]propyl, 4-[(2 or 5-)1,3,4-oxadiazolyl]butyl, 5-[(2 or 5-)1,3,4-oxadiazolyl]pentyl, 6-[(2 or 5-)1,3,4-oxadiazolyl]hexyl, 1,1-dimethyl-2-[(2 or 5-)1,3,4-oxadiazolyl]ethyl, 2-methyl-3-[(2 or 5-)1,3,4-oxadiazolyl]propyl, 2-oxo-[(3 or 5-)1,3,4-oxadiazolyl]methyl, 5-oxo-[(2 or 3-)1,3,4-oxadiazolyl]methyl, 2-[2-oxo-(3 or 5-)(1,3,4-oxadiazolyl)]ethyl, 1-[5-oxo-(2 or 3-)1,3,4-oxadiazolyl]ethyl, 3-[(2 or 5-)1,3,4-oxadiazolyl]propyl, 4-[2-oxo(3 or 5-)1,3,4-oxadiazolyl]butyl, 5-[5-oxo(2 or 3-)1,3,4-oxadiazolyl]pentyl, 6-[2-oxo(3 or 5-)1,3,4-oxadiazolyl]hexyl, 1,1-dimethyl-2-[5-oxo(2 or 3-)1,3,4-oxadiazolyl]ethyl, 2-methyl-3-[2-oxo(3 or 5-)1,3,4-oxadiazolyl]propyl groups.

Examples of the thienyl lower alkyl group include thienylalkyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as a (2 or 3-)thienylmethyl group, 2-[(2 or 3-)thienyl]ethyl group, 1-[(2 or 3-)thienyl]ethyl group, 3-[(2 or 3-)thienyl]propyl group, 4-[(2 or 3-)thienyl]butyl group, 5-[(2 or 3-)thienyl]pentyl group, 6-[(2 or 3-)thienyl]hexyl group, 1,1-dimethyl-2-[(2 or 3-)thienyl]ethyl group, and 2-methyl-3-[(2 or 3-)thienyl]propyl group.

Examples of the pyrimidinylcarbonyl group which may have an oxo group as a substituent on the pyrimidine ring include pyrimidinylcarbonyl groups which may have 1 to 3 oxo groups as substituents on the pyrimidine ring such as a (2,3,4 or 6-)pyrimidinylcarbonyl group, 2,6-dioxo-(1,3,4 or 5-)pyrimidinylcarbonyl group, 2-oxo-(1,3,4,5 or 6-)pyrimidinylcarbonyl group, 6-oxo-(1,2,3,4 or 5-)pyrimidinylcarbonyl group, 4-oxo-(1,2,3,4 or 6-)pyrimidylcarbonyl group, 2,4-dioxo-(1,3,4 or 6-)pyrimidinylcarbonyl group, and 2,4,6-trioxo-(1,3 or 5-)pyrimidylcarbonyl group.

Examples of the lower alkoxy lower alkoxy group include linear or branched alkoxy groups having 1 to 6 carbon atoms which may have a linear or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as a methoxymethoxy group, 1-ethoxyethoxy group, 2-methoxyethoxy group, 2-propoxyethoxy group, 3-isopropoxypropoxy group, 4-butoxybutoxy group, 5-pentyloxypentyloxy group, 6-hexyloxyhexyloxy group, 1,1-dimethyl-2-methoxyethoxy group, 2-methyl-3-ethoxypropoxy group, and 3-methoxypropoxy group.

Examples of the lower alkoxycarbonyl lower alkoxy group include alkoxycarbonylalkoxy groups of which both alkoxy moieties are linear or branched alkoxy groups having 1 to 6 carbon atoms such as methoxycarbonylmethoxy, ethoxycarbonylmethoxy, 2-methoxycarbonylethoxy, 2-ethoxycarbonylethoxy, 1-ethoxycarbonylethoxy, 3-methoxycarbonylpropoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy, 6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxycarbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, hexyloxycarbonylmethoxy groups.

Examples of the carboxy lower alkoxy group include carboxyalkoxy groups of which the alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms such as a carboxymethoxy group, 2-carboxyethoxy group, 1-carboxyethoxy group, 3-carboxypropoxy group, 4-carboxybutoxy group, 5-carboxypentyloxy group, 6-carboxyhexyloxy group, 1,1-dimethyl-2-carboxyethoxy group, and 2-methyl-3-carboxypropoxy group.

Examples of the phenoxy lower alkanoyl group include phenoxyalkanoyl groups of which the alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as a 2-phenoxyacetyl group, 3-phenoxypropionyl group, 2-phenoxypropionyl group, 4-phenoxybutyryl group, 5-phenoxypentanoyl group, 6-phenoxyhexanoyl group, 2,2-dimethyl-2-phenoxypropionyl group, and 2-methyl-3-phenoxypropionyl group.

Examples of the 1,2,3,4-tetrahydroquinolylcarbonyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring include 1,2,3,4-tetrahydroquinolylcarbonyl groups which may have 1 or 2 oxo groups as substituents on the tetrahydroquinoline ring such as a [(1,3,4,5,6,7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl group, [2-oxo-(1,3,4,5,6,7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl group, [4-oxo-(1,2,3,5,6,7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl group, and [2,4-dioxo-(1,3,5,6,7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl group.

Examples of the 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring include 1,2,3,4-tetrahydroquinolyl groups which may have 1 or 2 oxo groups as substituents on the tetrahydroquinoline ring such as a (1,2,3,4,5,6,7 or 8-)1,2,3,4-tetrahydroquinolyl group, 2-oxo-(1,3,4,5,6,7 or 8-)1,2,3,4-tetrahydroquinolyl group, 4-oxo-(1,2,3,5,6,7 or 8-)1,2,3,4-tetrahydroquinolyl group, and 2,4-dioxo-(1,3,5,6,7 or 8-)1,2,3,4-tetrahydroquinolyl group.

Examples of the amino group which may have a lower alkoxycarbonyl group as a substituent include amino groups which may have a linear or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms such as an amino group, methoxycarbonylamino group, ethoxycarbonylamino group, propoxycarbonylamino group, isopropoxycarbonylamino group, butoxycarbonylamino group, tert-butoxycarbonylamino group, pentyloxycarbonylamino group, and hexyloxycarbonylamino group.

Examples of the benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring include benzoyl groups which may have 1 to 3 linear or branched alkoxy groups having 1 to 6 carbon atoms as substituents on the phenyl ring such as a benzoyl group, 2-methoxybenzoyl group, 3-methoxybenzoyl group, 4-methoxybenzoyl group, 2-ethoxybenzoyl group, 3-ethoxybenzoyl group, 4-ethoxybenzoyl group, 4-isopropoxybenzoyl group, 3-butoxybenzoyl group, 4-pentyloxybenzoyl group, 4-hexyloxybenzoyl group, 3,4-dimethoxybenzoyl group, 3,4-diethoxybenzoyl group, 2,4-dimethoxybenzoyl group, 2,5-dimethoxybenzoyl group, 2,6-dimethoxybenzoyl group, and 3,4,5-trimethoxybenzoyl group.

Examples of the lower alkyl group which have 1 or 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group, and a lower alkylthio group include, in addition to the above described phenyl lower alkyl groups, linear or branched alkyl groups which have 1 to 6 carbon atoms which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, a phenyl group, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkylthio group having 1 to 6 carbon atoms such as 1,1-diphenylmethyl, 1,1-di(4-fluorophenyl)methyl, 1-phenyl-1-(4-methoxyphenyl)methyl, 3,3-diphenylpropyl, 2,5-difluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 3,5-difluorobenzyl, 2,6-difluorobenzyl, 3-trifluoromethylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 3,4-dimethoxybenzyl, 3,5-dimethoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 3,4-dimethylbenzyl, 2,3-dimethylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-cyanobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-methoxybenzyl, 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 2,5-dichlorobenzyl, 3,4-dichlorobenzyl, 2,6-dichlorobenzyl, 4-fluorobenzyl, 3-fluorobenzyl, 2-fluorobenzyl, 4-nitrobenzyl, 3-nitrobenzyl, 2-nitrobenzyl, 3-trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2-trifluoromethoxybenzyl, 4-methoxycarbonylbenzyl, 3-methoxycarbonylbenzyl, 4-tert-butylbenzyl, 4-ethylbenzyl, 4-isopropylbenzyl, 4-methoxy-3-chlorobenzyl, 2-(4-methoxyphenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methylphenyl)ethyl, 4-phenylbenzyl, 3,3-diphenylpropyl, 3-methyl-4-nitrobenzyl, 4-(4-methoxyphenyl)butyl, 2-(4-methylphenyl)ethyl, 4-tert-butoxycarbonylbenzyl, 3-chloro-6-methoxybenzyl, 4-nitro-3-methylbenzyl, 4-tert-butyrylbenzyl, 2-(2-ethoxycarbonylphenyl)ethyl, 1-(3-propoxycarbonylphenyl)ethyl, 3-(4-pentyloxycarbonylphenyl)propyl, 4-(3-hexyloxycarbonylphenyl)butyl, 5-(3,4-dimethoxycarbonylphenyl)pentyl, 6-(3,4,5-diethoxycarbonylphenyl)hexyl, 1,1-dimethyl-2-(4-butoxycarbonylphenyl)ethyl, 2-methyl-3-(4-methoxycarbonylphenyl)propyl, 2-(2-cyanophenyl)ethyl, 1-(3-cyanophenyl)ethyl, 3-(4-cyanophenyl)propyl, 4-(2-cyanophenyl)butyl, 5-(3-cyanophenyl)pentyl, 6-(4-cyanophenyl)hexyl, 1,1-dimethyl-2-(2,4-dicyanophenyl)ethyl, 2-methyl-3-(2,4,6-tricyanophenyl)propyl, 2-(2-nitrophenyl)ethyl, 1-(3-nitrophenyl)ethyl, 3-(4-nitrophenyl)propyl, 4-(2-nitrophenyl)butyl, 5-(3-nitrophenyl)pentyl, 6-(4-nitrophenyl)hexyl, 1,1-dimethyl-2-(2,4-dinitrophenyl)ethyl, 2-methyl-3-(2,4,6-trinitrophenyl)propyl, 2-(2-phenylphenyl)ethyl, 1-(3-phenylphenyl)ethyl, 3-(4-phenylphenyl)propyl, 4-(2-phenylphenyl)butyl, 5-(3-phenylphenyl)pentyl, 6-(4-phenylphenyl)hexyl, 1,1-dimethyl-2-(2,4-diphenylphenyl)ethyl, 2-methyl-3-(2,4,6-triphenylphenyl)propyl, 2-(2-fluorophenyl)ethyl, 1-(3-bromophenyl)ethyl, 3-(4-iodophenyl)propyl, 4-(2-bromophenyl)butyl, 5-(3-chlorophenyl)pentyl, 6-(4-bromophenyl)hexyl, 1,1-dimethyl-2-(2,4-dichlorophenyl)ethyl, 2-methyl-3-(2,4,6-trifluorophenyl)propyl, 2-(2-ethylphenyl)ethyl, 1-(3-propylphenyl)ethyl, 3-(4-butylphenyl)propyl, 4-(2-pentylphenyl)butyl, 5-(3-hexylphenyl)pentyl, 6-(4-trifluoromethylphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethyl)phenyl]propyl, 2-(2-ethoxyphenyl)ethyl, 1-(3-propoxyphenyl)ethyl, 3-(4-butoxyphenyl)propyl, 4-(2-pentyloxyphenyl)butyl, 5-(3-hexyloxyphenyl)pentyl, 6-(4-trifluoromethoxyphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethoxyphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethoxy)phenyl]propyl, 2-methylthiobenzyl, 3-methylthiobenzyl, 4-methylthiobenzyl, 3,4-dimethylthiobenzyl, 2,3-dimethylthiobenzyl, 2-(2-ethylthiophenyl)ethyl, 2-(4-methylthiophenyl)ethyl, 1-(3-propylthiophenyl)ethyl, 3-(4-butylthiophenyl)propyl, 4-(2-pentylthiophenyl)butyl, 5-(3-hexylthiophenyl)pentyl, 6-(4-methylthiophenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethylthiophenyl)ethyl, 2-methyl-3-[2,4,6-trimethylthiophenyl]propyl, 2-methyl-4-cyanobenzyl, 3-ethoxy-4-ethoxycarbonylbenzyl, 4-phenyl-3-nitrobenzyl, 3-fluoro-4-methoxybenzyl, 4-trifluoromethyl-3-cyanobenzyl, 3-trifluoromethoxy-3-fluorobenzyl groups.

Examples of the phenyl group which may have, on the phenyl ring, 1 to 3 groups selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms which may have a halogen atom as a substituent and a linear or branched alkyl group having 1 to 6 carbon atoms which may have a halogen atom as a substituent include phenyl groups which may have, on the phenyl ring, 1 to 3 groups selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents and a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxylphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-(bromomethoxy)phenyl, 3-(2-chloroethoxy)phenyl, 4-(2,3-dichloropropoxy)phenyl, 4-(4-fluorobutoxy)phenyl, 3-(5-chloropentyloxy)phenyl, 4-(5-bromohexyloxy)phenyl, 4-(5,6-dibromohexyloxy)phenyl, 3,4-di(trifluoromethoxy)phenyl, 3,4-di(4,4,4-trichlorobutoxy)phenyl, 2,4-di(3-chloro-2-methoxypropyl)phenyl, 2,5-di(3-chloropropoxy)phenyl, 2,6-di(2,2,2-trifluoroethoxy)phenyl, 3,4,5-tri(trifluoromethoxy)phenyl, 4-(2,2,2-trichloroethoxy)phenyl, 2-methyl-4-trifluoromethoxyphenyl, 3-ethyl-4-trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, 3-ethyl-4-trichloromethylphenyl groups.

Examples of the pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent include pyrrolidinylalkyl groups which may have, on the pyrrolidine ring, 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 hydroxyl groups as substituents and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1,2, or 3-)pyrrolidinyl]methyl, 2-[(1,2, or 3-)pyrrolidinyl]-ethyl, 1-[(1,2, or 3-)pyrrolidinyl]ethyl, 3-[(1,2, or 3-)pyrrolidinyl]propyl, 4-[(1,2, or 3-)pyrrolidinyl]-butyl, 5-[(1,2, or 3-)pyrrolidinyl]pentyl, 6-[(1,2, or 3-)pyrrolidinyl]hexyl, 1,1-dimethyl-2-[(1,2, or 3-)pyrrolidinyl]ethyl, 2-methyl-3-[(1,2, or 3-)pyrrolidinyl]propyl, [1-methyl-(2 or 3-)pyrrolidinyl]methyl, 2-[2-ethyl-(1,3,4, or 5-)pyrrolidinyl]ethyl, 1-[3-propyl-(1,2,4, or 5-)pyrrolidinyl]ethyl, 3-[1-butyl-(2 or 3-)pyrrolidinyl]propyl, 4-[2-pentyl-(1,3,4, or 5-)pyrrolidinyl]butyl, 5-[3-hexyl-(1,2,4, or 5-)pyrrolidinyl]pentyl, 6-[1,2-dimethyl-(3,4, or 5-)pyrrolidinyl]hexyl, 1,1-dimethyl-2-[1,2,3-trimethyl-(4 or 5-)pyrrolidinyl]ethyl, 2-methyl-3-[1-ethyl-2-methyl-(3,4, or 5-)pyrrolidinyl]propyl, [1-(2-hydroxyethyl)-(2 or 3-)pyrrolidinyl]methyl, [2-hydroxymethyl-(1,3,4, or 5-)pyrrolidinyl]methyl, 2-[2-hydroxymethyl-(1,3,4, or 5-)pyrrolidinyl]ethyl, 1-[3-(3-hydroxypropyl)-(1,2,4, or 5-)pyrrolidinyl]ethyl, 3-[l-(4-hydroxybutyl)-(2 or 3-)pyrrolidinyl]propyl, 4-[2-(5-hydroxypentyl)-(1,3,4, or 5-)pyrrolidinyl]butyl, 5-[3-(6-hydroxyhexyl)-(1,2,4, or 5-)pyrrolidinyl]pentyl, 6-[1,2-dihydroxymethyl-(3,4, or 5-)pyrrolidinyl]hexyl, 1,1-dimethyl-2-[1,2,3-trihydroxymethyl-(4 or 5-)pyrrolidinyl]ethyl, 2-methyl-3-[2-(1,2-hydroxyethyl)-(1,3,4, or 5-)pyrrolidinyl]propyl, [2-(2,3,4-trihydroxybutyl)-(1,3,4, or 5-)pyrrolidinyl]methyl groups.

Examples of the amino substituted lower alkyl group which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 substituents selected from the group consisting of a phenyl group and a linear or branched alkyl group having 1 to 6 carbon atoms such as aminomethyl, 2-aminomethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, N,N-diethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diisopropylaminoethyl, (N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl, phenylaminomethyl, 1-phenylaminoethyl, 2-phenylaminoethyl, 3-phenylaminopropyl, 4-phenylaminobutyl, 5-phenylaminopentyl, 6-phenylaminohexyl, N-methyl-N-phenylaminomethyl, 2-(N-ethyl-N-phenylamino)ethyl, (N-ethyl-N-phenylamino)methyl, 2-(N-methyl-N-phenylamino)ethyl groups.

Examples of the tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group include tetrahydrofurylalkyl groups which may have a hydroxyl group as a substituent on the lower alkyl group and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2 or 3-)tetrahydrofuryl]methyl, 2-[(2 or 3-)tetrahydrofuryl]ethyl, 1-[(2 or 3-)tetrahydrofuryl]ethyl, 3-[(2 or 3-)tetrahydrotetrahydrofuryl]propyl, 4-[(2 or 3-)tetrahydrofuryl]butyl, 5-[(2 or 3-)tetrahydrofuryl]pentyl, 6-[(2 or 3-)tetrahydrofuryl]hexyl, 1,1-dimethyl-2-[(2 or 3-)tetrahydrofuryl]ethyl, 2-methyl-3-[(2 or 3-)tetrahydrofuryl]propyl, 1-hydroxy-1-[(2 or 3-)tetrahydrofuryl]methyl, 2-hydroxy-2-[(2 or 3-)tetrahydrofuryl]ethyl, 2-hydroxy-1-[(2 or 3-)tetrahydrofuryl]ethyl, 3-hydroxy-3-[(2 or 3-)tetrahydrotetrahydrofuryl]propyl, 4-hydroxy-4-[(2 or 3-)tetrahydrofuryl]butyl, 5-hydroxy-5-[(2 or 3-)tetrahydrofuryl]pentyl, 6-hydroxy-6-[(2 or 3-)tetrahydrofuryl]hexyl, 2-hydroxy-1,1-dimethyl-2-[(2 or 3-)tetrahydrofuryl]ethyl, 3-hydroxy-2-methyl-3-[(2 or 3-)tetrahydrofuryl]propyl groups.

Examples of the phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group include, in addition to the above described phenoxy lower alkyl groups, phenoxyalkyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a nitro group and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 2-methylphenoxymethyl, 3-methylphenoxymethyl, 4-methylphenoxymethyl, 3,4-dimethylphenoxymethyl, 2,3-dimethylphenoxymethyl, 3,4,5-trimethylphenoxymethyl, 2-(2-ethylphenoxy)ethyl, 2-(3-methylphenoxy)ethyl, 2-(4-methylphenoxy)ethyl, 1-(3-propylphenoxy)ethyl, 3-(4-butylphenoxy)propyl, 4-(2-pentylphenoxy)butyl, 5-(3-hexylphenoxy)pentyl, 6-(4-methylphenoxy)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenoxy)ethyl, 2-methyl-3-(2,4,6-trimethylphenoxy)propyl, 2-(4-nitro-3-methylphenoxy)ethyl, 4-nitrophenoxymethyl, 3-nitrophenoxymethyl, 2-nitrophenoxymethyl, 2-(2-nitrophenoxy)ethyl, 2-(4-nitrophenoxy)ethyl, 1-(3-nitrophenoxy)ethyl, 3-(4-nitrophenoxy)propyl, 4-(2-nitrophenoxy)butyl, 5-(3-nitrophenoxy)pentyl, 6-(4-nitrophenoxy)hexyl, 1,1-dimethyl-2-(2,4-dinitrophenoxy)ethyl, 2-methyl-3-(2,4,6-trinitrophenoxy)propyl.

Examples of the phenyl lower alkanoyl group include phenylalkanoyl groups of which the alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as a 2-phenylacetyl group, 3-phenylpropionyl group, 2-phenylpropionyl group, 4-phenylbutyryl group, 5-phenylpentanoyl group, 6-phenylhexanoyl group, 2,2-dimethyl-3-phenylpropionyl group, and 2-methyl-3-phenylpropionyl group.

Examples of the 5- to 7-membered saturated heterocyclic group formed by mutually binding R20 and R21, R22 and R23, R26 and R27, R29 and R30 or R32 and R33 together with the nitrogen atoms bound to them, through or not through a nitrogen atom, a oxygen atom or a sulfur atom, include a pyrrolidinyl group, piperidinyl group, piperazinyl group, morpholino group, thiomorpholino group, and homopiperazinyl group.

Examples of the phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring include, in addition to the above described phenoxy lower alkyl groups, phenoxyalkyl groups which may have, on the phenyl ring, 1 to 3 linear or branched alkyls having 1 to 6 carbon atoms as substituents and of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 2-methylphenoxymethyl, 3-methylphenoxymethyl, 4-methylphenoxymethyl, 3,4-dimethylphenoxymethyl, 2,3-dimethylphenoxymethyl, 3,4,5-trimethylphenoxymethyl, 2-(2-ethylphenoxy)ethyl, 2-(4-methylphenoxy)ethyl, 1-(3-propylphenoxy)ethyl, 3-(4-butylphenoxy)propyl, 4-(2-pentylphenoxy)butyl, 5-(3-hexylphenoxy)pentyl, 6-(4-methylphenoxy)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenoxy)ethyl, 2-methyl-3-(2,4,6-trimethylphenoxy)propyl groups.

Methods for producing the compound of the present invention will be described below.

The compound of the present invention of the general formula (1) which have various Ys is produced, for example, as shown by the following reaction formulas 1 to 4.

In the formula, R1, R2, X1 and A are the same as described before, Y1 represents an O group, an S group or an NH group, and X2 represents a halogen atom.

The reaction between the compound (2) and the compound (3) is generally carried out in an appropriate solvent or without a solvent, and in the presence or absence of a basic compound.

Examples of the inert solvent used include aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, fatty acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, dimethylsulfoxide, N,N-dimethylformamide, N-methylpyrrolidone, and hexamethylphosphoric acid triamide, and a mixture thereof.

Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and cesium carbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide, sodium hydride, potassium hydride, potassium, sodium, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, and sodium n-butoxide, and organic bases such as pyridine, imidazole, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), and 1,4-diazabicyclo[2.2.2]octane (DABCO), and a mixture thereof.

When the reaction is carried out in the presence of a basic compound, the basic compound is used in an amount typically equimolar to the compound (2), and preferably 1 to 10 times of the compound (2) on a molar basis.

The compound (3) is used in an amount typically at least equimolar to the compound (2), and preferably 1 to 10 times of the compound (2) on a molar basis.

The reaction is carried out typically at −30 to 200 C., and preferably at about −30 to 150 C., and is generally completed in about 5 minutes to 80 hours.

To this reaction system, an alkali metal halide such as sodium iodide or potassium iodide may be added, and a phase-transfer catalyst may be added.

Examples of the phase-transfer catalyst include quaternary ammonium salts substituted with a group selected from the group consisting of a linear or branched alkyl group having 1 to 18 carbon atoms, a phenyl lower alkyl group which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and a phenyl group, such as tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium fluoride, tetrabutylammonium iodide, tetrabutylammonium hydroxide, tetrabutylammonium hydrogensulfite, tributylmethylammonium chloride, tributylbenzylammonium chloride, tetrapentylammonium chloride, tetrapentylammonium bromide, tetrahexylammonium chloride, benzyldimethyloctylammonium chloride, methyltrihexylammonium chloride, benzyldimethyloctadecanylammonium chloride, methyltridecanylammonium chloride, benzyltripropylammonium chloride, benzyltriethylammonium chloride, phenyltriethylammonium chloride, tetraethylammonium chloride, tetramethylammonium chloride; phosphonium salts substituted with a linear or branched having 1 to 18 carbon atoms such as tetrabutylphosphonium chloride; and pyridinium salts substituted with a linear or branched alkyl group having 1 to 18 carbon atoms such as 1-dodecanylpyridinium chloride. These phase-transfer catalysts are used singly or in a combination of two or more.

Typically the phase-transfer catalyst is used in an amount of 0.1 to 1 times of the compound (2), and preferably 0.1 to 0.5 times of the compound (2).

The compound (1a), wherein Y1 represents an NH group, may also be produced by reacting the compound (2) with the compound (3) in the presence of an acid in place of a base. Examples of the acid used here include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, and organic acids such as acetic acid, trifluoroacetic acid, and p-toluenesulfonic acid. These acids are used singly or as a mixture of two or more.

The compound (1), wherein Y represents an N(R5) group, and R5 is R5 other than a hydrogen atom, may be produced from the corresponding compound (1) wherein Y represents an NH group, as shown in the following reaction formula 2.


wherein R1, R2, X1, A and X2 are the same as described above, R5a represents a lower alkyl group, phenyl lower alkyl group or cycloalkyl group, R5b represents a hydrogen atom, lower alkyl group, phenyl group or phenyl lower alkyl group, R5c represents a lower alkanoyl group or benzoyl group. RB represents a hydrogen atom or lower alkyl group, and R5b and RB, together with carbon atoms bound to these groups, may form a cycloalkyl ring by binding each other, provided that the alkyl moiety in the CHRBR5b group of the compound (1d) has 1 to 6 carbon atoms.

The reaction of the compound (1b) with the compound (4) is carried out under the similar condition as that for the reaction of the compound (2) with the compound (3) as shown by the above described reaction formula 1.

The reaction of the compound (1b) with the compound (5) is carried out, for example, in the presence of a reducing agent without a solvent or with an appropriate solvent. Hereinafter, this method is called method A.

Examples of the solvent used here include water, lower alcohols such as, methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, acetonitrile, fatty acids such as formic acid, and acetic acid, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, aromatic hydrocarbons such as benzene, toluene, and xylene, and halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, and a mixture thereof.

Examples of the reducing agent include fatty acids and alkali metal salts thereof such as formic acid, sodium formate, and sodium acetate, hydride reducing agents such as sodium borohydride, sodium cyanoborohydride, sodium triacetyloxyborohydride, and aluminum lithium hydride, or a mixture of these hydride reducing agents, and catalytic hydrogen reducing agents such as palladium black, palladium-carbon, platinum oxide, platinum black, and Raney nickel.

In using a fatty acid or an alkali metal salt thereof such as formic acid, sodium formate, or sodium acetate as a reducing agent, the appropriate reaction temperature is typically from room temperature to about 200 C., and preferably about 50 to about 150 C., and the reaction is completed generally in about 10 minutes to 10 hours. It is preferable to use a fatty acid or an alkali metal salt thereof in a large excess amount with respect to the compound (1b).

In using a hydride reducing agent, the appropriate reaction temperature is typically −80 to 100 C., and preferably −80 to 70 C., and the reaction is completed in general in 30 minutes to 60 hours. The hydride reducing agent is used in an amount typically 1 to 20 times of the compound (1b), and preferably 1 to 6 times of the compound (1b) on a molar basis. Especially in using aluminum lithium hydride as a hydride reducing agent, it is preferable to employ an ether such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, or diglyme, or an aromatic hydrocarbon such as benzene, toluene, or xylene. To the reaction system, an amine such as trimethylamine, triethylamine, and N-ethyldiisopropylamine, or molecular sieves such as Molecular Sieves 3A (MS-3A) or Molecular Sieves 4A (MS-4A) may be added.

In using a catalytic hydrogen reducing agent, the reaction is preferably carried out in a hydrogen atmosphere typically at a normal pressure to about 20 atm, and preferably at a normal atmosphere to about 10 atm, or in the presence of a hydrogen donor such as formic acid, ammonium formate, cyclohexene, or hydrazine hydrate, at a temperature of typically −30 to 100 C., and preferably 0 to 60 C. The above described reaction is in general completed in about 1 to 12 hours. The catalytic hydrogen reducing agent is used typically in an amount of about 0.1% to 40% by weight, and about 1 to 20% by weight based on the compound (1b).

In the reaction of the compound (1b) with the compound (5), the compound (5) is typically used in an amount at least equimolar to the compound (1b), and preferably used in an equal amount to a large excess amount of compound (5) on a molar basis.

When the compound (5), wherein RB and R5b are mutually bound together with the carbon atoms which bind to these groups to form a cycloalkyl ring, is used as a starting material, and the hydride reducing agent is used to carry out the reaction, cycloalkyloxytrialkylsilane such as [(1-ethoxycyclopropyl)oxy]trimethylsilane may be used in place of the compound (5) as the starting material to produce the above described compound (5) in the reaction system.

The compound (1d) may be produced by reacting the compound (1b) with compound (5) under the reaction condition similar to the reaction condition of the compound (1f) with hydroxylamine of the later described reaction formula 3, and then reducing the resulting compound represented by the general formula:


wherein R1, R2, X1, RB and R5b are the same as described above.
A reaction condition similar to that of the method A may be applied to this reducing reaction.

The reaction of the compound (1b) with the compound (6) is carried out by a method for reacting the compound (1b) with carboxylic acid of the compound (6) in a typical reaction for producing an amide bond. Known reactions for producing an amide bond may be applied to this reaction for producing an amide bond. Specific methods thereof include: (a) a mixed acid anhydride method, specifically, a method of reacting an alkylhalocarboxylic acid with the carboxylic acid (6) to prepare a mixed acid anhydride, and then reacting the amine (1b) with the mixed acid anhydride; (b) an active ester method, specifically, a method of preparing, from the carboxylic acid (6), an active ester such as a phenyl ester, p-nitrophenyl ester, N-hydroxysuccinimide ester, or 1-hydroxybenzotriazole ester, or an active amide with benzoxazoline-2-thione, and then reacting the active ester or amide with the amine (1b); (c) a carbodiimide method, specifically, a method of condensation reaction of wherein the carboxylic acid (6) with the amine (1b) in the presence of an activator such as dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (WSC), or carbonyldiimidazole; (d) other methods, for example, a method of preparing carboxylic anhydride from the carboxylic acid (6) by the action of a dehydrator such as acetic anhydride, and then reacting the carboxylic anhydride with the amine (1b), a method of reacting an ester of the carboxylic acid (6) with a lower alcohol with the amine (1b) at a high pressure and a high temperature, and a method of reacting an acid halide of the carboxylic acid (6), that is, carboxylic acid halide, with the amine (1b).

The mixed acid anhydride used in the mixed anhydride method (a) described above, may be obtained by a typical Schotten-Baumann reaction, and the compound of the present invention of the general formula (1e) can be produced by reacting the amine (2) with the mixed acid anhydride without isolation.

The Schotten-Baumann reaction described above is carried out in the presence of a basic compound.

The basic compounds used include compounds commonly used in Schotten-Baumann reaction, for example, organic bases such as triethylamine, trimethylamine, pyridine, dimethylaniline, N-ethyldiisopropylamine, dimethylaminopyridine, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7, and 1,4-diazabicyclo[2.2.2]octane (DABCO), and inorganic bases such as carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide, potassium hydride, sodium hydride, potassium, sodium, sodium amide, and metal alcoholates such as sodium methylate and sodium ethylate. These basic compounds are used singly or in a combination of two or more. The reaction is carried out at typically about −20 to 100 C., and preferably about 0 to 50 C., and the reaction time is about 5 minutes to 10 hours, and preferably about 5 minutes to 2 hours.

The resulting mixed acid anhydride is reacted with the amine (1b) at typically about −20 to 150 C., preferably about 10 to 50 C., and the reaction time is about 5 minutes to 10 hours, and preferably about 5 minutes to 5 hours.

The mixed acid anhydride method is, in general, carried out in a solvent. Any of the solvent conventionally used for the mixed acid anhydride method may be used. Specific examples of the solvent include halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon, tetrachloride, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dimethoxyethane, esters such as methyl acetate, ethyl acetate, and isopropyl acetate, and aprotic polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, and hexamethylphosphoric acid triamide, and a mixture thereof.

Examples of the alkylhalocarboxylic acid used in the mixed acid anhydride method include methyl chloroformate, methyl bromoformate, ethyl chlorformate, ethyl bromoformate, and isobutyl chloroformate.

In the mixed acid anhydride method, it is typically preferable to use the carboxylic acid (6), alkylhalocarboxylic acid and the amine (1b) equimolar to each other. However, each of alkyl halocarboxylic acid and the carboxylic acid (6) may be used 1 to 1.5 times of the amine (1b) on a molar basis, respectively.

In the above described method (c) of condensation reaction in the presence of an activator, the reaction is carried out in an appropriate solvent in the presence or absence of a basic compound. Any of the solvents and basic compounds used in the reaction in the other methods (d) described above of reacting carboxylic acid halide with the amine may be used for this reaction. It is appropriate to use the activator in an amount typically at least equimolar to the compound (1b), and preferably 1 to 5 times of the compound (1b) on a molar basis. When WSC is used as an activator, the reaction may be carried out advantageously by adding 1-hydroxybenzotriazole and/or an acid such as hydrochloric acid. This reaction is carried out at typically about −20 to 180 C., and preferably about 0 to 150 C., and is completed typically in about 5 minutes to 90 hours.

In the other method (d) described above, wherein the amine (1b) is reacted with carboxylic acid halide, the reaction is carried out in an appropriate solvent in the presence of a basic compound. As such a basic compound, known basic compounds may be widely used, and, for example, any of compounds used for the Shotten-Baumann reaction described above may be used. Examples of the solvent include, in addition to the solvents used in the mixed acid anhydride method described above, alcohols such as methanol, ethanol, isopropanol, propanol, butanol, 3-methoxy-1-butanol, ethyl cellosolve, and methyl cellosolve, acetonitrile, pyridine, acetone, and water. The ratio of the amine (1b) to the carboxylic acid halide in the reaction is not specified and may be appropriately selected in a wide range. Typically, the former may be used in an amount at least about equimolar to the latter, and preferably about 1 to 5 times of the latter on a molar basis. This reaction is carried out at typically about −20 to 180 C., and preferably about 0 to 150 C., and is completed typically in 5 minutes to 50 hours.

Further, the reaction for producing an amide bond shown in the above described reaction formula 2 may be carried out by reacting the carboxylic acid (6) and the amine (1b) in the presence of a condensation agent of a phosphorus compound such as triphenylphosphine, diphenylphosphinyl chloride, phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate, diethyl cyanophosphate, diphenylphosphoric acid azide, or bis(2-oxo-3-oxazolidinyl)phosphinic chloride. The condensation agent described above is used singly or in a combination of two or more.

The above described reaction is carried out, in the presence of the solvent and the basic compound which are used in the method for reacting the carboxylic acid halide with the amine (1b) described above, at typically about −20 to 150 C., and preferably about 0 to 100 C., and is completed typically in 5 minutes to about 30 hours. The condensation agent and the carboxylic acid (6) may be used respectively in an amount at least about equimolar to the amine (1b), and preferably about 1 to 2 times of the amine (1b) on a molar basis.

The compound (1), wherein Y represents a CH(OH) or C(═NOH) group, is produced from the corresponding compound wherein Y represents a CO group, as shown in the reaction formula 3.


wherein R1, R2, X1 and A are the same as described above.

The compound (1g) is produced by reducing the compound (1f).

In the reducing reaction described above, a reducing method employing a hydride reducing agent is favorably used. Examples of the reducing agent used include aluminum lithium hydride, sodium borohydride, borane, diborane, and lithium borohydride-trimethoxyborane. These reducing agents are used singly or in a mixture of two or more. The reducing agent may be used in an amount typically at least equimolar to the compound (1f), and preferably 1 to 15 times of the compound (1f) on a molar basis. This reducing reaction is typically carried out in an appropriate solvent, for example, water, a lower alcohol such as methanol, ethanol, or isopropanol, an ether such as tetrahydrofuran, diethyl ether, diisopropyl ether, or diglyme, or a halogenated hydrocarbon such as dichloromethane, chloroform, or carbon tetrachloride, or a mixture thereof, at about −60 to 150 C., preferably from about −30 to 100 C., in general for about 10 minutes to 40 hours. In the case where aluminum lithium hydride or borane is used as the reducing agent, it is preferable to use an anhydrous solvent of tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, or the like.

The compound (1h) is produced by reacting the compound (1f) and hydroxylamine in an appropriate inert solvent in the presence or absence of a basic compound.

Examples of the basic compound used in this reaction include inorganic basic compounds such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, and potassium carbonate, fatty acid alkali metal salts such as sodium acetate, organic bases such as piperidine, piperidinium acetate, triethylamine, trimethylamine, pyridine, dimethylaniline, N-ethyldiisopropylamine, dimethylaminopyridine, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), and 1,4-diazabicyclo[2.2.2]octane (DABCO). These basic compounds may be used singly or in a mixture of two or more.

Any of inert solvents which do not have adverse effects on the reaction may be used. Examples thereof include water, aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, fatty acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, dimethyl sulfoxide, N,N-dimethylformamide, and hexamethyl phosphate triamide, and a mixture thereof.

Hydroxylamine is used in an amount typically at least equimolar to the compound (1f), and preferably 1 to 5 times of the compound (1f) on a molar basis. The reaction temperature is typically at room temperature to 200 C., and preferably about 50 to 150 C., and the reaction is in general completed in about 5 minutes to 30 hours.

The compound (1), wherein Y represents an S(O)n group (n=1 or 2), is produced from the corresponding compound wherein Y represents an S group, as shown in the reaction formula 4.


wherein R1, R2, X1 and A are the same as described above, A16 represents a -A group or a -A10-T2-COOR59a group, T2 represents an N(R17)B3 group, a B19N(R18) group, a B4 group, a -Q-B5 group, a B6N(R19)B7 group, a COB10 group, a CH(OH)B11 group, a B23aCO group, or a direct bond, wherein R17, B3, B19, R18, B4, B5, B6, R19, B7, B10 and B11 are the same as described above, A10 represents a group of the formula:


wherein R3 and p are the same as described above, provided that the a is bound to a S group or a S(O)j group, and the b is bound to -T2,
R59a is a hydrogen atom or a lower alkyl group, and j is 1 or 2.

The reaction for converting the compound (1zzzz) into the compound (1aaaaa) is carried out in an appropriate solvent and in the presence of an oxidizing agent.

Examples of the solvent include water, fatty acids such as formic acid, acetic acid, and trifluoroacetic acid, alcohols such as methanol and ethanol, and halogenated hydrocarbons such as chloroform and dichloromethane, and a mixture thereof.

Examples of the oxidizing agent include peracids such as performic acid, peracetic acid, pertrifluoroacetic acid, perbenzoic acid, m-chloroperbenzoic acid, and o-carboxyperbenzoic acid, hydrogen peroxide, sodium metaperidodate, dichromic acid, dichromates such as sodium dichromate and potassium dichromate, permanganic acid, permanganates such as sodium permanganate and potassium permanganate, and lead salts such as lead tetraacetate. These oxidizing agents are used singly or in a mixture of two or more.

The oxidizing agent is appropriately used in an amount typically at least equimolar to the compound (1zzzz), and preferably 1 to 2 times of the compound (1zzzz) on a molar basis. In the oxidizing reaction which converts a sulfur atom into a sulfonyl group (j=2), it is appropriate to use the oxidizing agent in an amount typically at least two times of the compound (1zzzz), and preferably 2 to 4 times of the compound (1zzzz) on a molar basis.

The above described reaction is carried out at typically −10 to 150 C., and preferably about −10 to 100 C. and is, in general, completed in about 1 to 100 hours.

The compound of the present invention, which has the general formula (1) with various As, is produced, for example, as shown in the following reaction formulas 5 to 36.

The compound (1), wherein A represents a group of the formula:


wherein R4 represents an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which may have an oxo group as a substituent on the pyrimidine ring, a 1,2,4-oxadiazolyl lower alkyl group which may have an lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, or a -(T)l-NR14R15 group, wherein T is a lower alkylene group and l is 1, is produced by reacting the compound (7) with the compound (8) as shown in the reaction formula 5.


wherein R1, R2 Y1 and X1 are the same as described above, A1 represents a group of the formula:


wherein R3 and p are the same as described above, R37a represents a B21X2 group, B21 represents a lower alkylene group, and X2 is the same as described above, and A2 represents a group of the formula:


wherein R3 and p are the same as described above, R38 represents a B21R4a group, B21 is the same as described above, R4a represents an imidazolyl group, a 1,2,4-triazolyl group, a 1,2,3-triazolyl group, a 1,2,5-triazolyl group, a pyrazolyl group, a pyrimidinyl group which has an oxo group as a substituent on the pyrimidine ring, a 1,2,4-oxadiazolyl group which may have as a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl group which may have an oxo group as a substituent on the thiazolidine ring, or an NR14R15 group, and R14 and R15 are the same as described above.

The reaction of the compound (7) with the compound (8) is carried out under the reaction condition similar to that of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The compound (1), wherein A represents a group of the formula:


wherein R4 is an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which has an oxo group as a substituent on the pyrimidine ring, a 1,2,4-oxadiazolyl lower alkyl group which has a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group which has an oxo group as a substituent on the thiazolidin ring, or a (T)l-NR14R15 group, wherein T is a lower alkylene group and l is 1, is also produced by reacting the compound (8) with the compound (9) as shown in the reaction formula 6.


wherein R1, R2, X1 and Y1 and R4a are the same as described above, A3 represents a group of the formula:


wherein R3 and p are the same as described above, R39 represents a (B21)fCORA group, B21 is the same as described above, RA represents a hydrogen atom or a lower alkyl group, and f represents 0 or 1, and A4 represents a group of the formula:


wherein R3 and p are the same as described above, R40 represents a (B21)fCHRAR4a group, and B21, RA, f and R4a are the same as described above, provided that the alkyl moiety of the (B21)fCHRAR4a group has not more than 6 carbon atoms.

The reaction of the compound (9) with the compound (8) is carried out under the same condition as in the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

The compound (1), wherein A represents a group of the formula:


wherein R4 represents a 3,5-dioxoisooxazolidinyl lower alkylidene group which may have an oxo group as a substituent on the 3,5-dioxoisooxazolidine ring, is produced by reacting the compound (11) with the compound (10) as shown in the reaction formula 7.


wherein R1, R2, X1 and Y are the same as described above,
A5 represents a group of the formula:


wherein R3 and p are the same as described above, R41 represents a B22(CO2R4)(CO2R44) group, B22 represents a lower alkylidene group, and R43 and R44 represent a lower alkyl group, and
A6 represents a group of the formula:


wherein R3 and p are the same as described above, and R42 represents


wherein B22 is the same as described above.

The reaction of the compound (10) with the compound (11) is carried out under the same condition as that of the reaction which converts the compound (1f) into the compound (1h) of the reaction formula 3.

The compound (1), wherein A represents a group of the formula:


wherein R4 represents a group of the formula:


is produced from the compound (13), as shown in the reaction formula 8.


wherein R1, R2, X1, Y and R13 are the same as described above,
A7 represents of the formula:


wherein R3 and p are the same as described above, and
R45 represents a halogen atom,
A8 represents a group of the formula:


wherein R3 and p are the same as described above, and
R46 represents


wherein R13 is the same as described above,
A9 represents a group of the formula:


wherein R3 and p are the same as described above, and
R47 represents a group of the formula:


wherein R13 is the same as described above, and
A8a represents a group of the formula:


wherein R3 and p are the same as described above, and
R46′ represents a group


wherein R13 is the same as described above.

The reaction of the compound (13) with the compound (12) is carried out in an appropriate inert solvent in the presence of a basic compound.

Examples of the basic compound used here include such as sodium, potassium, magnesium, sodium hydride, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, and potassium tert-butoxide, and alkyl and aryl lithiums or lithium amides such as methyl lithium, n-butyl lithium, phenyl lithium, and lithium diisopropylamide. These basic compounds are used singly or in a mixture of two or more.

The basic compound is appropriately used in an amount typically at least equimolar to the compound (13), and preferably 1 to 5 times of the compound (13) on a molar basis.

Examples of the inert solvent used include aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, aliphatic hydrocarbons such as n-hexane, heptane, and cyclohexane, halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride, dimethylsulfoxide, and N,N-dimethylformamide, and a mixture thereof.

The reaction is carried out at typically about −90 to 150 C., and preferably about −90 to 120 C., and is completed in general in about 10 minutes to 10 hours.

The compound (12) is appropriately used in an amount typically at least equimolar to the compound (13), and preferably 1 to 5 times of the compound (13) on a molar basis.

The reaction which converts the compound (1l) into the compound (1m) is carried out in an appropriate inert solvent and in the presence of an acid.

Examples of the acid used here include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, and organic acids such as sulfonic acids including p-toluenesulfonic acid. These acids are used singly or in a mixture of two or more.

It is appropriate to use the acid typically in an amount at least equimolar to the compound (11), and preferably in an equal amount to a large excess amount with respect to the compound (11) on a molar basis.

Any of the inert solvents used in the reaction of the compound (13) with the compound (12) may be used in this reaction.

This reaction is suitably carried out at typically room temperature to 200 C., preferably room temperature to about 150 C., and is completed in general in about 1 to 20 hours.

The reaction which converts the compound (1l) into the compound (1l′) is carried out in an appropriate solvent and in the presence of an acid and a catalyst.

Examples of the solvent used include water, lower alcohols such as methanol, ethanol, and isopropanol, ketones such as acetone and methyl ethyl ketone, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, diisopropyl ether, diglyme, and 1,4-dioxane, aromatic hydrocarbons such as benzene, toluene, and xylene, acetonitrile, dimethyl sulfoxide, N,N-dimethylacetamide, N,N-dimethylformamide, and N-methylpyrrolidone, and a mixture thereof.

Examples of the acid used here include inorganic acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, and organic acids such as boron trifluoride diethyl etherate, formic acid, acetic acid, trifluoroacetic acid, and p-toluenesulfonic acid.

Examples of the catalyst include alkylsilane compounds such as triethylsilane.

The acids and the catalysts described above are respectively used typically in an amount about 0.01 to 5 times of the compound (1l), and preferably about 0.01 to 1 time of the compound (1l) on a molar basis.

The above described reaction is carried out at about room temperature to 200 C., and preferably about room temperature to 150 C., and is completed in general in about 1 to 10 hours.

The reaction which converts the compound (1l) into the compound (1l′) may be carried out in an appropriate solvent and in the presence of a catalytic hydrogen reducing agent.

Examples of the solvent used include water, fatty acids such as acetic acid, alcohols such as methanol, ethanol, and isopropanol, aliphatic hydrocarbons such as n-hexane, alicyclic hydrocarbons such as cyclohexane, ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, monoglyme, diglyme, and 1,4-dioxane, esters such as methyl acetate, ethyl acetate, and butyl acetate, and aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and a mixture thereof.

Examples of the catalytic hydrogen reducing agent include palladium, palladium-black, palladium-carbon, palladium hydroxide-carbon, rhodium-alumina, platinum, platinum oxide, copper chromite, Raney nickel, and palladium acetate.

The catalytic hydrogen reducing agent is used typically in an amount of 0.01 to 1 times of the compound (1l) on a weight basis.

The above described reaction favorably proceeds at typically about −20 to 100 C., and preferably about 0 to 80 C., and is completed generally in about 0.5 to 20 hours, and the hydrogen pressure is typically at 1 to 10 atm.

It is preferable to add a mineral acid such as hydrochloric acid to this reaction system.

The compound (1), wherein A represents a group of the formula:


wherein R4 represents a group of the formula:


wherein R13 represents a group other than a hydrogen atom, is produced from the corresponding compound wherein R13 is a hydrogen atom, as shown in the following reaction formula 9.


wherein R1, R2, X1, Y, A10, RA, R13a and X2 are the same as described above, provided that the a and the b of A10 are bound to Y and the piperidinyl group, respectively, R13b represents a lower alkyl group which may have a halogen atom as a substituent, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a piperazinylcarbonyl lower alkyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or a morpholinocarbonyl substituted lower alkyl group,
R13c represents a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkoxy carbonyl group, a benzoyl group, a morpholino substituted alkanoyl group, a piperazinyl lower alkanoyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group on the phenyl ring; or an imidazolyl lower alkanoyl group, and
R13d represents a hydrogen atom, a lower alkyl group which may have a halogen atom as a substituent, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a phenyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl group, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a piperazinylcarbonyl lower alkyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or a morpholinocarbonyl substituted lower alkyl group,
provided that the alkyl moiety of the side chain (CHRAR13d) of the compound (1q) has not more than 6 carbon atoms.

The reaction of the compound (1n-1) with the compound (13′) is carried out under the condition similar to that of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (1n-1) with the compound (14) is carried out under the condition similar to that of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (1n-1) with the compound (15) is carried out under the condition to similar that of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

Also, the reaction of the compound (1n-2) with the compound (13′) is carried out under the condition similar to that of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2, the reaction of the compound (1n-2) with the compound (14) is carried out under the condition similar to that of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2, and the reaction of the compound (1n-2) with the compound (15) is carried out under the condition to similar that of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the reaction formula 9, the hydrolysis of the compounds (1o-1) and (1o-2), wherein R13b represents a lower alkoxycarbonyl lower alkyl group, may produce the corresponding compounds (1o-1) and (1o-2), wherein R13b represents a carboxy lower alkyl group.

In the reaction formula 9, the hydrolysis of compounds (1p-1) and (1p-2), wherein R13c represents a lower alkoxycarbonyl group, may produce the corresponding compounds (1p-1) and (1p-2), wherein R13c is a hydrogen atom.

The hydrolysis reaction (hereinafter this hydrolysis reaction is called hydrolysis B) may be carried out in an appropriate solvent or without a solvent, in the presence of an acidic or basic compound.

Examples of the solvent used include water, lower alcohols such as methanol, ethanol, isopropanol, and tert-butanol, ketones such as acetone and methyl ethyl ketone, ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme, and diglyme, fatty acids such as acetic acid and formic acid, esters such as methyl acetate and ethyl acetate, halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride, dimethylsulfoxide, N,N-dimethylformamide, and hexamethylphosphoric acid triamide, and a mixture thereof.

Examples of the acid include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, organic acids such as formic acid, acetic acid, trifluoroacetic acid, sulfonic acids including p-toluenesulfonic acid, and Lewis acids such as boron tribromide and boron trichloride. These acids are used singly or in a mixture of two or more.

Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate, and metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and lithium hydroxide. These basic compounds are used singly or in a mixture of two or more.

The hydrolysis reaction is favorably carried out at typically about 0 to about 200 C., and preferably about 0 to 150 C., and is completed in general in about 10 minutes to 50 hours.

The compound (1), wherein A represents a group of the formula:


wherein R4 represents a group of the formula:


wherein R13 represents an imidazolyl lower alkyl group, is produced as shown in the following reaction formula 10.


wherein R1, R2, X1, Y, A10, R13a, B21 and X2 are the same as described above, provided that the a and b of A10 are bound to Y and the piperidinyl group, respectively.

The reaction of the compound (1r-1) with the compound (16) with and the reaction of the compound (1r-2) with the compound (16) are carried out under the condition similar to that of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The compound (1), wherein A represents a group of the formula:


wherein R4 represents a group of the formula:


wherein R13 represents a morpholino substituted alkanoyl group, a piperazinyl lower alkanoyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which has a lower alkylenedioxy group as a substituent on the phenyl ring, or an imidazolyl lower alkanoyl group, may be produced from the corresponding compound, wherein R13 represents a lower alkanoyl group which may have a halogen atom as a substituent, as shown in the following reaction formula 11.


wherein R1, R2, X1, Y, R13a, B21 and X2 are the same as described above, and R47′ is a morpholino group, a piperazinyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or an imidazolyl group, provided that the a and b of A10 are bound to Y and the piperidinyl group, respectively.

The reaction of the compound (1t-1) with the compound (17) and the reaction of the compound (1t-2) with the compound (17) are carried out under the condition similar to that of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The compound (1), wherein A represents a group of the formula:


wherein R4 represents a group of the formula:


wherein R13 represents a piperazinylcarbonyl lower alkyl group which is substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or a morpholinocarbonyl substituted lower alkyl group, is produced from the corresponding compound, wherein R13 is a carboxy group, as shown in the following reaction formula 12.


wherein R1, R2, X1, Y, A10, R13a, and B21 are the same as described above, R48 is a piperazinyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or a morpholino group, provided that the a and b of A10 are bound to Y and the piperidinyl group, respectively.

The reaction of the compound (1v-1) with the compound (18) and the reaction of the compound (1v-2) with the compound (18) are carried out under the condition similar to that of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The compound (1), wherein A represents a group of the formula:


wherein R4 represents -(T)l-NR14R15, is produced as shown in the reaction formulas 13 and 14.

In the formula, R1, R2, X1, Y, A10, X2, l, R14 and R15 are the same as described above, T1 is a lower alkylene group, COB8, SO2 or a CH(OH)B9, and B8 and B9 are the same as described above, provided that, in the compounds (35) and (1pp), the a and b of A10 are bound to Y and -(T1)1, respectively.

The reaction of the compound (35) with the compound (36) is carried out in the reaction condition similar to that of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The compound (35), wherein l is 0, may also be produced by reacting the corresponding compound (35) with the compound (36) in an appropriate solvent in the presence of a basic compound and a catalyst.

Any of the solvents and basic compounds which are used in the reaction of the compound (2) with the compound (3) of the above described reaction formula 1 may be used here.

Examples of the catalyst to be used include various metal complexes as well as various combinations of a metal complex with ligand. Examples of the metal complex include, for instance, palladium acetate (II), tetrakis(triphenylphosphine)palladium (0), tris(dibenzylideneacetone)dipalladium (0) and the like. Examples of the ligand include, for instance, R-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (R-BINAP), S-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (S-BINAP), RAC-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (RAC-BINAP), t-butylphosphine, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and the like.

The catalyst is appropriately used in an amount typically at least equimolar to the compound (35), and preferably 1 to 5 times of the compound (35) on a molar basis.

This reaction is carried out at typically about 0 to 200 C., and preferably about 0 to 150 C., and is completed in general in about 1 to 60 hours. This reaction is called reaction C hereinafter.

In the formula, R2, X1, Y, A10, T2, R14 and R15 are the same as described above, provided that, in the compounds (37) and (1qq), the a and b of A10 are bound to Y and T2, respectively, and R95 represents R1 or a halogen atom.

The reaction of the compound (37) with the compound (36) is carried out in the reaction condition similar to that of the reaction of the compound (1b) with the compound (6) in the above described reaction formula 2.

The compound (1), wherein A represents a group of the formula:


wherein R4 represents -(T)l-NR14R15, and l represents 0, may also be produced by the method shown in the reaction formula 15.


wherein R1, R2, XI, Y, RA, X2, T, l, and A10, are the same as described above, R49 is the same group as R15 defined in (15), (22), (23), (27) and (36a), R49a is R15 defined in (2) to (5), (7), (8), (10), (11), (13), (14), (16) to (21), (24), (25), (26), (26a), (27a), (28a), (29a), (30a), (31a), (32a), (33a), (34a), (35a), or (37a), a phenoxycarbonyl group and a lower alkylsulfonyl group, R49b represents a hydrogen atom, an alkyl group which may have a hydroxyl group as a substituent, a phenoxy lower alkyl group, a phenyl lower alkyl group which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group, a phenyl group which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a phenyl group which may have a lower alkylenedioxy group on the phenyl ring, a lower alkoxycarbonyl substituted lower alkyl group, a carboxy substituted lower alkyl group, a cycloalkyl lower alkyl group, a cycloalkyl group, a pyridyl lower alkyl group, a pyridyl group, an amino group substituted lower alkyl group which may have a substituent selected from the group consisting of a lower alkyl group and a lower alkanoyl group, a lower alkoxy lower alkyl group, an imidazolyl group, an imidazolyl lower alkyl group, a 1,2,3,4-tetrahydroisoquinolylcarbonyl substituted lower alkyl group, an A group-substituted carbonyl lower alkyl group, a pyrrolidinyl group, a pyrrolidinyl lower alkyl group, a morpholino group, a morpholino lower alkyl group, an anilinocarbonyl lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a piperazinyl group which may have, on the piperazine ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a piperazinyl lower alkyl group which may have, on the piperazine ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an amidino group which may have a lower alkyl group as a substituent, an amidino lower alkyl group which may have a lower alkyl group as a substituent, a B group substituted carbonyl lower alkyl group, or a cyano substituted lower alkyl group,
R14a represents a hydrogen atom or a lower alkyl group which may have a hydroxyl group as a substituent, and
R34, d, R36, R37 and B20 are the same as described above, provided that, in the compounds (1rr), (1ss), (1ss′) and (1ss″), the a and b of A10 are bound to Y and N, respectively, and, in the compound (1ss″), the CHRAR49b moiety of the side chain, (Y-A10N(R14a)(CHRAR49b), has not more than 6 carbon atoms.

The reaction of the compound (1rr) with the compound (38a) is carried out under the condition to similar that of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (1rr) with the compound (38) is carried out under the condition similar to that of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (1rr) with the compound (38b) is carried out under the condition similar to that of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2 described above.

The compound (1), wherein A represents a group of the formula:


wherein R4 represents a -(T)l-NR14R15 group, 1 represents 1, and T represents a CH(OH)B9 group, may also be produced by the method shown in the following reaction formula 16.


wherein R1, R2, X1, A10, Y, B8, B9, R14, and R15 are the same as described above, provided that, in the compounds (1tt) and (1uu), the a and b of A10 are bound to Y and B8 or B9, respectively.

The reaction which converts the compound (1tt) into the compound (1uu) is carried out under the similar condition similar to that of the reaction which converts the compound (1f) into the compound (1g) of the above described reaction formula 3.

The compound (1), wherein A represents a group of the formula:


wherein R4 represents a -(T)l-NR14R15 group, 1 represents 1, and T represents a CH(OH)B11CO group, may also be produced by the method shown in the following reaction formula 17.


wherein R1, R2, X1, A10, Y, B10, B11, R14 and R15 are the same as described above, provided that, in the compounds (1vv) and (1ww), the a and b of A10 are bound to Y and a COB10 or CH(OH)B11 group, respectively.

The reaction which converts the compound (1vv) into the compound (1ww) is carried out under the condition similar to that of the reaction which converts the compound (1f) into the compound (1g) of the above described reaction formula 3.

The compound (1), wherein A represents a group of the formula:


wherein R4 is a -(T)lNR14R15 group, and R14 and R15 are bound with each other to form a 5- to 10-membered saturated or unsaturated heterocyclic group which has various substituents thereon, may be produced as shown in the following reaction formulas 18 to 20, 22, 24 to 31, and 34 to 36.

In the formula, R1, R2, RB, X1, Y, T, l, A10 and X2 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14b and R15a represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one secondary amine thereon;

R14c and R15b represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one tertiary amine thereon substituted with R50;

R14d and R15c represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one tertiary amine thereon substituted with R51;

R14e and R15d represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one tertiary amine thereon substituted with a R52(RB)CH group;

R14f and R15e represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one tertiary amine thereon substituted with a group of the formula:


R50 is the same substituent of the heterocyclic ring, which is formed by R14 and R15 bound each other, as the above described (28), (30), (31), (32), (33), (34), (36), (37), (38), (41), (43), (44), (45), (47), (49) (provided that t is 1), (50) (provided that o is 0), (51), (52), (53), (54), (55), (56), (57), (58), (59), (60), (62), (63), (64), (65), (66), (70), (77), (79), (82), (83), (87), (88a), or (90a);
R51 is the same substituent of the heterocyclic group, which is formed by R14 and R15 bound each other, as the above described (35), (39), (40), (42), (50) (provided that o is 1), (67), (75), (76), (77), (78), (80), (81) or (84) (provided that s is 0);
R52 is a hydrogen atom, a lower alkyl group which has 1 or 2 phenyls which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group and which may have a pyridyl group on the lower alkyl group, a phenyl group which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxy group, and a lower alkylenedioxy group, a pyridyl lower alkyl group which may be substituted on the pyridine ring with 1 to 3 substituents selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl groups as a substituent, a pyridyl group which may be substituted on the pyridine ring with 1 to 3 substituents selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent, a pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as substituents on the pyrrole ring, a pyrrolyl group which may have 1 to 3 lower alkyl groups as substituents on the pyrrole ring, a benzoxazolyl lower alkyl group, a benzoxazolyl group, a benzthiazolyl lower alkyl group, a benzothiazolyl group, a furyl lower alkyl group, a furyl group, a lower alkyl group which may have a substituent selected from the group consisting of a hydroxyl group and a halogen atom, a naphtyl lower alkyl group, a naphthyl group, a phenoxy lower alkyl group, a B12CONR20R21 group; a B13NR22R23 group, a 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a 1,2,3,4-tetrahydronaphthyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a quinolyl lower alkyl group, a quinolyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,3,4-tetrazolyl group which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a thiazolyl lower alkyl group which may have a phenyl group as a substituent on the thiazole ring, a thiazolyl group wherein may have a phenyl group as a substituent on the thiazole ring, a benzoyl lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom, a piperidinyl lower alkyl group which may have a lower alkoxy group as a substituent on the piperidine ring, a benzoyl lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom, a piperidinyl group which may have a lower alkyl group on the piperidine ring, a 1,2,3,4-tetrahydroquinolyl lower alkyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, a 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, a 1,3,4-oxadiazolyl lower alkyl group which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, a 1,3,4-oxadiazolyl group which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, a cycloalkyl lower alkyl group, a cycloalkyl group, a thienyl lower alkyl group, a thienyl group, a lower alkoxy lower alkyl group, a carboxy lower alkyl group, a lower alkoxycarbonyl lower alkyl group, an imidazolyl lower alkyl group, or an imidazolyl group; and
RB and R52, together with carbon atoms to which they bind, may form a cycloalkyl group or a tetrahydro-4H-pyranyl group;
provided that the alkyl moiety of the R52(RB)CH group in the compound (1aaa) has not more than six carbon atoms.

The reaction of the compound (35′) with the compound (39) is carried out under the condition similar to that of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (35′) with the compound (40) is carried out under the condition similar to that of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (35′) with the compound (41) is carried out under the condition similar to that of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

When the reaction is carried out using the compound (41) as a starting material, wherein RB and R52 together with carbon atoms bound to them form a cycloalkyl ring or a tetrahydro-4H-pyran ring using a hydride reducing agent, a cycloalkyloxytrialkylsilane such as [(1-ethoxycyclopropyl)oxy]trimethylsilane may be used as a starting material in place of the compound (41) to generate the above described compound (41) in the reaction system.

The reaction of the compound (35′) with the compound (42) is carried out under the condition to similar that of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The compound (35′) may also be produced from the compound (1yy), (1zz) or (1aaa) under the reaction condition similar to that of the reaction which converts the compound (1iii′) into the compound (1hhh′) of the later described reaction formula 24.

In the formula, R1, R2, X1, Y, T, l, A10 and X2 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14g and R15f are a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one tertiary amine thereon substituted with a lower alkoxycarbonyl group; and
R14h and R15g are a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one secondary amine thereon.

The reaction which converts the compound (1ccc) into the compound (1ddd) may be carried out under the reaction condition similar to that of the hydrolysis B described for the above described reaction formula 9.

In the formula, R74a represents a nitro group or a R1 group, and R1, R2, X1, Y, T, l and A10 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14i and R15h are a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one lower alkoxycarbonyl lower alkoxy group, lower alkoxycarbonyl group, lower alkoxycarbonyl lower alkyl group, or (B12CO)t-N(R20a)R51′ group thereon;
R14j and R15i are a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one carboxy lower alkoxy group, carboxy group, carboxy lower alkyl group, or (B12CO)t-N(R20a)R52′ group thereon;
B12 and t are the same as described above;
R20a represents a hydrogen atom, a cycloalkyl group, an amino group which have a lower alkoxycarbonyl group as a substituent, a benzoyl group which may have 1 to 3 alkoxy groups as substituents on the phenyl ring, a lower alkyl group, a lower alkyl group which has 1 or 2 phenyls which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of an lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group, a phenyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a cycloalkyl lower alkyl group, a pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, an amino substituted lower alkyl group which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group, a 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a naphthyl lower alkyl group, a pyridyl lower alkyl group, a quinolyl lower alkyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group, a phenyl lower alkanoyl group, a lower alkanoyl group which may have a halogen atom as a substituent, an imidazolyl lower alkanoyl group, a lower alkoxycarbonyl lower alkyl group, a pyridyl group, or a carboxy lower alkyl group;
R51′ is a lower alkoxycarbonyl group or a lower alkoxycarbonyl lower alkyl group;
R52′ is a hydrogen atom or a carboxy lower alkyl group; and
R53 is a lower alkyl group.

The reaction which converts the compound (1eee) into the compound (1fff) may be carried out under the reaction condition similar to that of the hydrolysis B as described in the above described reaction formula 9.

Any of the reaction conditions for typical esterification reaction may be used for the reaction of the compound (1fff) with the compound (43). For example, the above described reaction is carried out in the presence of a mineral acid such as hydrochloric acid or sulfuric acid, and a halogenation agent such as thionylchloride, phosphorus oxychloride, phosphorus pentachloride, or phosphorus trichloride. The compound (43) is used in large excess over the compound (1fff). The above described reaction favorably proceeds at typically about 0 to 150 C., preferably about 50 to 100 C., and is completed in general in about 1 to 10 hours. The esterification described above may be carried out using a condensation agent such as carbodiimide in the presence of a basic compound such as dimethylaminopyridine. A typical reaction condition for generating an amide bond, which is used in the reaction of the compound (1b) with the compound (6) in the reaction formula 2, may also be used.

The reaction of the compound (1fff) with compound (43) may also be carried out in the presence of the same basic compound and the solvent as those used in the reaction of the compound (2) with the compound (3) of the reaction formula 1. The reaction is carried out at typically about 0 to 100 C., and preferably about 0 to 70 C., and is completed in general in about 1 to 30 hours.

The compound (1eee) may also be produced using a halogenated lower alkyl such as methyl iodide in place of the compound (43) under the condition similar to that of the reaction of the compound (2) with the compound (3) of the reaction formula 1.

In the formula, R1, R2, X1, Y, A10, R13a, B21 and R53 are the same as described above, and R54 is a lower alkyl group, provided that the a and b of A10 are bound to Y and the piperidinyl group, respectively.

The reaction which converts the compound (1ggg-1) into the compound (1v-1) and the reaction which converts the compound (1ggg-2) into the compound (1v-2) may be carried out under the reaction condition similar to that of the hydrolysis B described for the above described reaction formula -9, respectively.

The reaction of the compound (1v-1) with the compound (43) and the reaction of the compound (1v-2) with the compound (43) is carried out under the reaction condition similar to that of the reaction of the compound (1fff) with the compound (43) of the above described reaction formula 20.

The compound (1ggg-1) may also be produced using a halogenated lower alkyl such as methyl iodide in place of the compound (43) under the condition similar to that of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

Similarly, the compound (1ggg-2) may also be produced using a halogenated lower alkyl such as methyl iodide in place of the compound (43) under the condition similar to that of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula, R1, R2, X1, Y, T, l and A10 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14k and R15i are a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one B21CONHNH2 group, wherein B21 is the same as described above, thereon; and
R14l and R15k are a 5- to 10-membered saturated or unsaturated heterocyclic ring the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one group of the formula:


thereon.

The reaction which converts the compound (1hhh) into compound (1iii) is carried out under the condition similar to that of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R1, R2, X1, Y. A10, B21 and X2 are the same as described above, the a and b of A10 are bound to Y and (T)l, respectively, R55 is a lower alkanoyl group, and R55a is a lower alkyl group.

The reaction of the compound (44) with the compound (45) is carried out under the condition to similar that of the reaction which converts the compound (1f) into the compound (1h) of the above described reaction formula 3.

The reaction of the compound (44a) with the compound (46) is carried out under the condition similar to that of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The reaction which converts the compound (47) into the compound (1rrr) is carried out under the condition similar to that of the reaction which converts the compound (1f) into the compound (1h) of the above described reaction formula 3.

In the formula, R1, R2, XI, Y, T, l, A10 and X2 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14m and R15l are a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one hydroxyl group or hydroxyl group substituted lower alkyl group thereon;
R14n and R15m are a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one OR56 group thereon;
R56 represents a phenyl group which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a cyano group, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkyl group which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, a pyridyl lower alkyl group, a lower alkyl group, a lower alkoxy lower alkyl group, a benzoyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group; or a B15CONR26R27 group, wherein B15, R26 and R27 are the same as described above,
provided that, the R56 of the compound (48), which reacts with the above described heterocyclic group substituted with at least one hydroxyl group substituted lower alkyl group of the compound (1hhh′), is an unsubstituted phenyl group or a lower alkyl group.

The reaction of the compound (1hhh′) with the compound (48) is carried out under the condition similar to that of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The reaction which converts the compound (1iii′) into the compound (1hhh′) may be carried out under the condition to similar that of the hydrolysis B described in the above described reaction formula 9.

The compound (1iii′) may be converted into the compound (1hhh′) by a reduction reaction. This reduction reaction is, for example, carried out in an appropriate solvent in the presence of a catalytic hydrogen reducing agent.

Examples of the solvent used include water, fatty acids such as acetic acid, alcohols such as methanol, ethanol, and isopropanol, aliphatic hydrocarbons such as hexane and cyclohexane, ethers such as dioxane, tetrahydrofuran, diethyl ether, monoglyme, and diglyme, esters such as ethyl acetate and methyl acetate, aprotic polar solvents such as N,N-dimethylformamide, and a mixture thereof.

Examples of the catalytic hydrogen reducing agent used include palladium, palladium black, palladium-carbon, platinum, platinum oxide, copper chromite, and Raney nickel. These reducing agents may be used singly or as a mixture of two or more.

The catalytic hydrogen reducing agent is favorably used generally in an amount of 0.02 to 1 time of the compound (1iii′) on a weight basis.

The reaction temperature is typically at about −20 to 100 C., and preferably at about 0 to about 80 C. The reaction is preferably carried out at a hydrogen pressure of typically 1-10 atm, and is completed in general in about 0.5 to 20 hours.

In the formula R1, R2, X1, Y, T, l, A10, RA and X2 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14o and R15n are a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one (B12CO)tNHR20a group thereon;

R14p and R15o are a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one (B12CO)tN(R20a)R21b group thereon; and

R14q and R15p are a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic group has at least one (B12CO)tN(R20a)R21c group thereon;

R14r and R15q represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15 except that the heterocyclic ring has at least one (B12CO) tN(R20a)(CHRAR21d) group thereon,

wherein B12, t and R20a are the same as described above;

R21b represents a lower alkyl group, a cycloalkyl group, a lower alkyl group which have 1 or 2 phenyls which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent and a lower alkylthio group, a phenyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent, a cycloalkyl lower alkyl group, a pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, an amino substituted lower alkyl group which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group, a 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a naphthyl lower alkyl group, a pyridyl lower alkyl group, a quinolyl lower alkyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group, a lower alkoxycarbonyl lower alkyl group, a pyridyl group, or a carboxy lower alkyl group;
R21c represents a benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring, a lower alkoxycarbonyl group, a phenyl lower alkanoyl group, a lower alkanoyl group which may have a halogen atom as a substituent or an imidazolyl lower alkanoyl group; and
R21d represents a hydrogen atom, a lower alkyl group, a lower alkyl group which have 1 or 2 phenyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent and a lower alkylthio group, a phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may be substituted with a halogen atom, a lower alkoxy group which may be substituted with a halogen atom and a lower alkylthio group, a cycloalkyl lower alkyl group, a cycloalkyl group, a pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, a pyrrolidinyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, an amino substituted lower alkyl group which may have a group selected from the group consisting of a phenyl group and a lower alkyl group, a 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a 1,2,3,4-tetrahydronaphthyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a naphthyl lower alkyl group, a naphthyl group, a pyridyl lower alkyl group, a pyridyl group, a quinolyl lower alkyl group, a quinolyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,3,4-tetrazolyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,4-triazolyl group, a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group, a tetrahydrofuryl group which may have a hydroxyl group as a substituent on the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group, a lower alkoxycarbonyl lower alkyl group or a carboxy lower alkyl group;
provided that the alkyl moiety of CHRAR21d in the side chain ((B21CO)tN(R20a)(CHRAR21d)) has not more than 6 carbon atoms.

The reaction of the compound (1uuu) with the compound (49) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (1uuu) with the compound (51) is carried out under reaction conditions similar to those of the reaction of the compound (1b) and the compound (5) of the above described reaction formula 2.

The reaction of the compound (1uuu) with the compound (50) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R1, R2, X1, Y, T, l, and A10 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14s and R15r represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one (CO)oB13X2 group thereon;

R14t and R15s represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one (CO)o B13R84 group thereon; and

R84 is an NR22R23 group or an imidazolyl group;

wherein B13, o, X2, R22 and R23 are the same as described above.

The reaction of the compound (1yyy) with the compound (52) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

In the formula, R1, R2, X1, Y, T, l, and A10 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14s′ and R15r′ represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one N(R28)COB16X2 group thereon; and

R14u and R15t represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one N(R28)COB16NR29R30 group thereon;

wherein R28, B16, X2, R29 and R30 represent the same as described above.

The reaction of the compound (1aaaa) with the compound (53) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

In the formula, R74a, R2, X1, Y, T, l, and A10 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14v and R15u represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one B12COOH group thereon; and

R14w and R15v represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one B12CONR20R21 group thereon;

wherein B12, R20 and R21 are the same as described above.

The reaction of the compound (1cccc) with the compound (54) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R1, R2, X1, Y, T, l, and A10 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14x and R15w represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one OB15COOH group thereon; and

R14y and R15x represent a 5- to 10-membered saturated or unsaturated heterocyclic group as defined for the above described R14 and R15, except that the heterocyclic ring has at least one OB15CONR26R27 group thereon;

wherein B15, R26 and R27 are the same as described above.

The reaction of the compound (1eeee) with the compound (55) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.


are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;
R14z and R15y represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one N(R31)B17COOH group thereon; and
R14aa and R15z represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one N(R31)B17CONR32R33 group thereon;
wherein R31, B17, and R32, R33 are the same as described above.

The reaction of the compound (1gggg) with the compound (56) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R1, R2, X1, Y, T, l, and A10 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14bb and R15aa represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one COOH group thereon; and

R14cc and R15bb represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one CONR26R27 group thereon;

wherein R26 and R27 are the same as described above.

The reaction of the compound (1iiii) with the compound (57) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R1, R2, X1, Y, T, l, R14a and A10 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

h represents 0 or 1; and

R57 represents a lower alkoxycarbonyl group.

The reaction which converts the compound (1kkkk) into the compound (1llll) may be carried out under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

In the formula, R1, R2, X1, R3, R4, Y, R11 and R12 are the same as described above, R58 represents a lower alkyl group, and g represents 0 or 1.

The reaction which converts the compound (1mmmm) into the compound (1nnnn) may be carried out under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

The reaction of the compound (1nnnn) with the compound (58) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R1, R2, X1, Y, T, l, A10 and X2 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14hh and R15gg represent a 5- to 10 membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one (CO)o-B13NH(R22a) group thereon;

R14ii and R15hh represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one (CO)o-B13N(R22a)R23a group thereon;

R14jj and R15ii represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one (CO)o-B13N(R22a)R23b group thereon;

R14kk and R15jj represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one (CO)o-B13N(R22a)(CHRAR23c) group thereon,

wherein RA, B13 and o are the same as described above;

R22a is a hydrogen atom, a lower alkyl group, a benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group or a phenyl group;
R23a represents a lower alkyl group, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group or a phenyl group;
R23b represents a benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring; and
R23c represents a hydrogen atom, a lower alkyl group, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group or a phenyl group; provided that the alkyl moiety of the CHRAR23c group in the side chain ((CO)o-B13N(R22a)(CHRAR23c)) of the compound (1ssss) has not more than 6 carbon atoms.

The reaction of the compound (1pppp) with the compound (59) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (1pppp) with the compound (61) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

The reaction of the compound (1pppp) with the compound (60) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R1, R2, X1, Y, T, l, A10 and X2 are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R14ll and R15kk represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one (OB15)s-CONH(R26a) group thereon;

R14mm and R15ll represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one (OB15)s-CON(R26a)(R27a) group thereon;

R14nn and R15mm represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one (OB15)s-CON(R26a)(CHRAR27b) group,

wherein B15, s and RA are the same as described above;

R26a represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group or an imidazolyl lower alkyl group;

R27a represents a lower alkyl group, a phenyl lower alkyl group or an imidazolyl lower alkyl group; and

R27b represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, a phenyl group, an imidazolyl group or an imidazolyl lower alkyl group;

provided that the alkyl moiety of the CHRAR27b group in the side chain ((OB15)s-CO(R26a)(CHRAR27b)) of the compound (1vvvv) has not more than 6 carbon atoms.

The reaction of the compound (1tttt) with the compound (62) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (1tttt) with the compound (63) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R1, R2, X1, Y, T, l, A10, R14v, R15u, R14k and R14j are the same as described above, provided that the a and b of A10 are bound to Y and (T)l, respectively;

R59 represents a lower alkyl group; and

R14oo and R15nn represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one B21CONHNHCOOR59 group,

wherein B21 is the same as described above.

The reaction of the compound (1cccc′) with the compound (102) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction which converts the compound (1yyyy) into the compound (1hhh) may be carried out under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

The compound of the present invention of the general formula (1) having various R1s is produced, for example, as shown by the following reaction formulas 37 to 46.

In the formula, R2, X1, Y, A16, R6, R6, B21, RA and X2 are the same as described above, provided that the B21CHRA moiety of the (R6B21CHRA) group of the compound (1y) has not more than 6 carbon atoms.

The reaction of the compound (19) with the compound (20) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (19) with the compound (21) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

The reaction of the compound (19) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R2, X1, Y, A, R6, B, RA and X2 are the same as described above, R8a represents a lower alkyl group which may have a lower alkoxy group as a substituent, a lower alkylsulfonyl group or a phenyl lower alkyl group, R8b represents a hydrogen atom, a phenyl group, phenyl lower alkyl group or a lower alkyl group which may have a lower alkoxy group as a substituent, and R8c represents a lower alkanoyl group, provided that the alkyl moiety of the CHRAR8b group of the compound (1cc) has not more than 6 carbon atoms.

The reaction of the compound (1aa) with the compound (23) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (1aa) with the compound (24) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

The reaction of the compound (1aa) with the compound (25) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R2, X1, Y, A, B21, f, RA and R6 are the same as described above, provided that the (B21)fCHRA moiety of the ((B21)fCHRANHR6) group of the compound (1ee) has not more than 6 carbon atoms.

The reaction of the compound (26) with the compound (27) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R88 represents a Y-A group or a halogen atom, and R2, X1, Y, A, and R6, are the same as described above.

The reaction of the compound (28) with the compound (27) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R2, X1, Y, A, R6, R8a, R8b, R8c, RA and X2 are the same as described above, provided that the alkyl moiety of the CHRAR8b group of the compound (1hh) has not more than 6 carbon atoms.

The reaction of the compound (1ff′) with the compound (23) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (1ff′) with the compound (24) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

The reaction of the compound (1ff′) with the compound (25) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R2, X1, Y, A, R6 and X2 are the same as described above.

The reaction which converts the compound (30) into the compound (1jj) may be carried out under reaction conditions similar to those of the reaction which converts the compound (1f) into the compound (1h) of the above described reaction formula 3.

The reaction which converts the compound (1jj) into the compound (1kk) may be carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

The reaction of the compound (30) with the compound (32) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

In the formula, R2, X1, Y, A, X2 and R6 are the same as described above, B23 represents a lower alkylene group or a lower alkenylene group, and the B23HC═CH moiety in the side chain (R6B23HC═CH) in the compound (1mm) has 1 to 3 double bonds and has not more than 6 carbon atoms.

The reaction of the compound (33) with the compound (34) is carried out in an appropriate inert solvent and in the presence of a condensation agent.

Examples of the inert solvent used in the above described reaction include aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, fatty acids such as α-dimethylaminoacetic acid and acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, 1-methyl-2-pyrrolidone, pyridine, dimethyl sulfoxide, dimethylformamide, and hexamethylphosphoric acid triamide, and a mixture thereof.

Examples of the condensation agent include palladium complexes such as bis(benzonitrile)dichloropalladium (II).

The condensation agent is appropriately used in an amount typically 0.01 to 1 times, and preferably 0.01 to 0.5 times of the compound (33) on a molar basis.

The above described reaction favorably proceeds typically at 0 to 200 C., and preferably at about room temperature to about 150 C. and is, in general, completed in about 10 minutes to 20 hours.

The above described reaction proceeds advantageously by adding a alkali metal salt of fatty acid such as sodium acetate to the reaction system.

In the formula, R26, X1, Y, A and R6 are the same as described above.

The reaction which converts the compound (1nn) into the compound (1oo) may be carried out under reaction conditions similar to those of the reaction which converts the compound (1f) into the compound (1g) of the above described reaction formula 3.

In the formula, A17 represents a group of the formula:


wherein R2, R3, p, X1, Y, A, Bo and R6 are the same as described above.

The reaction of the compound (64) with the compound (65) is carried out in an appropriate solvent in the presence of a condensation agent.

Any of the solvents, which are used in the reaction of carboxylic acid halide with amine (1b) by the method (d) of the formula 2 for reacting the compound (1b) with the compound (6) (reaction which produces an amide bond), may be used in this reaction.

Examples of the condensation agent used include a mixture of an azocarboxylate (such as diethyl azodicarboxylate) with a phosphorus compound (such as triphenylphosphine).

The condensation agent is appropriately used in an amount typically at least equimolar to the compound (64), and preferably 1 to 2 times of the compound (64) on a molar basis.

The compound (65) is appropriately used in an amount typically at least equimolar to the compound (64), and preferably 1 to 2 times of the compound (64) on a molar basis.

The above described reaction favorably proceeds typically at 0 to 200 C., preferably at around 0 to 150 C. and is, in general, completed in around 1 to 10 hours.

In the formula, R2, X1, Y, A, and R6 are the same as described above.

The reaction of the compound (30) with the compound (66) is carried out in the presence or absence of a basic compound, and preferably in the absence of the basic compound in an appropriate solvent or without a solvent.

Any of the inert solvents and the basic compounds, which are used in the reaction of carboxylic acid halide with amine (1b) by the method (d) of the formula 2 for reacting the compound (1b) with the compound (6) (reaction which produces an amide bond), may be used in this reaction.

The compound (66) may be used in an amount typically at least about 1 to 5 times, and preferably about 1 to 3 times of the compound (30) on a molar basis.

The above described reaction is carried out typically at 0 to 200 C., and preferably at around room temperature to 150 C. and is, in general, completed in around 5 minutes to 50 hours.

A boron compound such as a boron trifluoride-diethyl ether complex may be added to the system of the above described reaction.

In the formula, R2, X1, Y, T2, A10, R14, R15, B21, RA, X2, R6 and R59 are the same as described above, provided that the a and b of A10 are bound to Y and T2, respectively.

The reaction which converts the compound (68) into the compound (71) may be carried out under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

The reaction of the compound (71) with the compound (100) is carried out under reaction conditions similar to those of the reaction of the compound (1fff) with the compound (43) in formula 20 as described above.

The compound (68) may also be produced using a halogenated lower alkyl group such as methyl iodide in place of the compound (100) in a reaction similar to the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The reaction which converts the compound (68) into the compound (69) may be carried out, for example, (1) by reducing the compound (0.68) with a catalytic hydride reducing agent in an appropriate solvent, or (2) by reducing the compound (68) with a reducing agent such as a mixture of a metal or a metal salt with an acid, or a mixture of a metal or a metal salt with an alkali metal hydroxide, a sulfide, an ammonium salt or the like, in an appropriate inert solvent.

Examples of the solvent in using the method (1) include water, acetic acid, alcohols such as methanol, ethanol, and isopropanol, hydrocarbons such as n-hexane and cyclohexane, ethers such as dioxane, tetrahydrofuran, diethyl ether, and diethylene glycol dimethyl ether, esters such as ethyl acetate and methyl acetate, and aprotic polar solvents such as N,N-dimethylformamide, and a mixture thereof. Examples of the catalytic hydride reducing agent used include palladium, palladium black, palladium-carbon, platinum-carbon, platinum, platinum oxide, copper chromite, and Raney nickel. These reducing agents may be used singly or in a mixture of two or more. In general, the reducing agent may be used in an amount 0.02 to 1 times of the compound (68) on a weight basis. The reaction temperature is typically about −20 to 150 C., and preferably about 0 to 100 C., and the hydrogen pressure is typically at 1 to 10 atm. In general, the above described reaction is completed in about 0.5 to 100 hours. An acid such as hydrochloric acid may be added to the above described reaction system.

The reducing agent which may be used in using the method (2) is a mixture of iron, zinc, tin or stannous chloride with a mineral acid such as hydrochloric acid or sulfuric acid; or a mixture of iron, ferrous sulfate, zinc or tin with an alkali metal hydroxide such as sodium hydroxide, a sulfate such as ammonium sulfate or an ammonium salt such as ammonium hydroxide or ammonium chloride. Examples of the inert solvent include water, acetic acid, alcohols such as methanol and ethanol, and ethers such as dioxane, and a mixture thereof. The reaction conditions may be chosen appropriately depending on the reducing agent used. For example, when stannous chloride or hydrochloric acid is used as the reducing agent, the reaction is appropriately carried out advantageously at about 0 to 150 C., and for around 0.5 to 10 hours. The above described reducing agent is used in an amount at least equal molar to the compound (68), and typically 1 to 5 times of the compound (68) on a molar basis.

The reaction of the compound (69) with the compound (20) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (69) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (69) with the compound (21) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

The reaction which converts the compound (69) into the compound (37a), the reaction which converts the compound (70a) into the compound (37d), the reaction which converts the compound (70b) into the compound (37c) and the reaction which converts the compound (70c) into the compound (37b) may be carried out under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

The reaction of the compound (71) with the compound (36) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (69) with the compound (32) is carried out under reaction conditions similar to those of the reaction of the compound (30) with the compound (32) in the reaction formula 42 as described above.

In the formula, R2, X1, Y, A10, B3, R14, R15, RA, R74a and X2 are the same as described above;

RC represents a CONR14R15 group or COOR59b group, R59b represents a lower alkyl group or a phenyl lower alkyl group;

R17a represents a lower alkyl group, a cycloalkyl group, a lower alkyl sulfonyl group or a lower alkenyl group;

R17b represents a hydrogen atom or a lower alkyl group; and

R17c represents a cycloalkylcarbonyl group, a lower alkanoyl group which may have a halogen atom as a substituent or an amino substituted lower alkanoyl group which may have a lower alkyl group as a substituent; wherein the a of A10 is bound to the Y group and the b is bound to an NHB3Rc group, N(R17a) B3Rc group, N(CH(RA)(R17b))B3Rc group or N(R17c)B3Rc group.

The reaction of the compound (72a) with the compound (73) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (72a) with the compound (75) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (72a) with the compound (74) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, Y, A10, B3, R14 and R15 are the same as described above, R17d represents a lower alkanoyl group which is substituted with a halogen atom, R60 represents an amino group which may be substituted with a lower alkyl group, and R61 represents an amino substituted lower alkanoyl group which may be substituted with a lower alkyl group, wherein the a of A10 is bound to the Y group and the b is bound to an N(R17d)B3CONR14R15 group or NR61B3CONR14R15 group.

The reaction of the compound (72e) with the compound (76) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) in the reaction formula 1 as described above.

In the formula, R2, X1, Y, R6, B21, RA and X2 are the same as described above, and All represents a group of the formula:


wherein R3 and p are the same as described above, provided that the alkyl moiety in the side chain (NHCH(RA)(B21R6) group) of the compound (78b) has not more than 6 carbon atoms.

The reaction which converts the compound (77a) into the compound (77b) may be carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

The reaction of the compound (77b) with the compound (20) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (77b) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (77b) with the compound (21) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R1, R2, X1, Y and A11 are the same as described above, and i represents an integer of 2 to 4.

In general, the reaction of the compound (77c) with the compound (79) is called Friedel-Crafts reaction and is carried out in an appropriate solvent in the presence of a Lewis acid.

Any of the Lewis acids typically used in the Friedel-Crafts reaction may be used here. Examples of these Lewis acids include aluminum chloride, zinc chloride, iron chloride, tin chloride, boron tribromide, and concentrated sulfuric acid. These Lewis acids are used singly or in a mixture of two or more. The Lewis acid is used typically in an amount 2 to 6 times of the compound (77c) on a molar basis.

Examples of the solvent used here include aromatic hydrocarbons such as carbon disulfide, nitrobenzene, and chlorobenzene, and halogenated hydrocarbons such as dichloromethane, dichloroethane, carbon tetrachloride, and tetrachloroethane, and a mixture thereof.

The compound (79) is typically used in an amount at least equimolar to the compound (77c), and preferably 1 to 5 times of the compound (77c) on a molar basis.

Typically the above described reaction proceeds favorably at 0 to 120 C., and preferably about 0 to 70 C., and is generally completed in about 0.5 to 24 hours.

In the formula, R2, X1, Y, R6, X2, B21 and RA are the same as described above. A12 represents a group of the formula:


R3 and p are the same as defined above, and
R62 represents a lower alkanoyl group or a hydroxyl group substituted lower alkyl group, provided that the alkyl moiety in the side chain (NHCH(RA)(B21R6) group) of the compound (81b) has not more than 6 carbon atoms.

The reaction which converts the compound (80a) into the compound (80b) is carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

The reaction of the compound (80b) with the compound (20) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (80b) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (80b) with the compound (21) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R1, R2, X1, and Y are the same as above,

A13 represents a group of the formula:


wherein R3 and p are the same as described above, and R63a represents a lower alkanoyl group or a lower alkyl group, and
A14 represents a group of the formula:


wherein R63b represents a lower alkanoyl group which is substituted with a halogen atom at the α-position or a lower alkyl group which is substituted with a halogen atom at the 2 position.

The reaction which converts the compound (80b′) into the compound (35a) is carried out in the presence of a halogenating agent in an appropriate solvent.

Examples of the halogenating agent include halogen atoms such as bromine and chlorine, iodine chloride, sulfuryl chloride, copper compounds such as cupric bromide, and N-halogenated succinic acid imides such as N-bromosuccinic acid imide and N-chlorosuccinic acid imide.

Examples of the solvent used include halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, fatty acids such as acetic acid and propionic acid, and carbon disulfide.

The halogenated agent is appropriately used in an amount typically 1 to 10 times, and preferably 1 to 5 times of the compound (80b′) on a molar basis.

The above described reaction is carried out typically at 0 C. to the boiling point of the solvent, and preferably at about 0 to 100 C., and is completed typically in about 5 minutes to 30 hours.

When an N-halogenated succinic acid imide is used as a halogenated agent, a peroxide such as benzoyl peroxide may be added to the reaction system as a initiator for the radical reaction.

In the formula, R2, X1, Y, A10, T2, R59, R8a, R8b, R8c, X2 and RA are the same as described above, and R64 represents a phenyl lower alkoxycarbonyl group, provided that the alkyl moieties in the side chain (N(CHRAR8b)(R64) group) of the compound (84b) and the side chain (NH(CHRAR8b) group) of the compound (84e) have not more than 6 carbon atoms, respectively, and the a and b of A10 are bound to the Y group and the T2 group, respectively.

The reaction of the compound (83) with the compound (23) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (69) with the compound (82), and the reaction of the compound (83) with the compound (25) are carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (83) with the compound (24) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

The reactions which respectively convert the compound (84a) into the compound (84d), the compound (84b) into the compound (84e), and the compound (84c) into the compound (84f) are carried out under reaction conditions similar to those of the reaction which converts the compound (1iii′) into the compound (1hhh′) by reduction as described for the above described reaction formula 24.

In the formula, R2, X1, Y, A10, B21, R4 and X2 are the same as described above, provided that the a and b of A10 are bound to the Y group and the B21 group, respectively.

The reaction which converts the compound (85) into the compound (7′) is carried out by reacting compound (85) to a halogenating agent in an appropriate solvent or without solvent.

Examples of the halogenating agent include mineral acids such as hydrochloric acid and hydrobromic acid, N,N-diethyl-1,2,2-trichlorovinyl azide, phosphorus pentachloride, phosphorus pentabromide, phosphorus oxychloride, sulfonyl halide compounds such as thionyl chloride, mesyl chloride, and tosyl chloride, and a mixture of carbon tetra bromide with triphenylphosphine. The sulfonyl halide compound is used together with a basic compound.

Any of the basic compounds used in the reaction of the compound (2) with the compound (3) of the reaction formula 1 may be used.

Examples of the solvent used include ethers such as dioxane, tetrahydrofuran, and diethyl ether, halogenated hydrocarbons such as chloroform, methylene chloride, and carbon tetrachloride, and dimethylformamide, and a mixture thereof.

When a sulfonyl halide compound is used together with a basic compound as a halogenating agent, the sulfonyl halide compound is appropriately used in an amount typically at least equimolar to the compound (85), and preferably 1 to 2 times of the compound (85) on a molar basis. The basic compound is used typically in a catalytic amount of the compound (85), and preferably in a catalytic amount to an amount equimolar to the compound (85). When another halogenating agent is used, such a halogenating agent is used at least equimolar to the compound (85), and typically used in a large excess amount.

The above described reaction proceeds favorably typically at room temperature to 200 C., and preferably at room temperature to 150 C., and in general is completed in about 1 to 80 hours.

In the formula, R74a, R2, X1, Y, A10 and B21 are the same as described above, and R65 represents a tri-lower alkyl silyl group, provided that the a and b of A10 are bound to the Y group and the B21 group, respectively.

Here, examples of the tri-lower alkyl silyl group include trialkylsilyl groups of which the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as

a tert-butyldimethylsilyl group, trimethylsilyl group, and diethylmethylsilyl group.

The reaction which converts the compound (86) into the compound (85) may be carried out under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

In the formula, R74a, R2, X1, Y, A10, B21, R65 and X2 are the same as described above, and R66 represents a hydrogen atom, a lower alkyl group or a lower alkoxycarbonyl group, provided that the a and b of A10 are bound to Y and B21, respectively, and the alkyl moieties in the side chain (Y-A10-B21CH2OH) of the compound (85a) and the side chain (Y-A10-B21CH2OR65) of the compound (86a) have not more than 6 carbon atoms.

The reaction which converts the compound (69a) into the compound (85a) is carried out under the similar reaction conditions as the reaction which converts the compound (1f) into the compound (1g) of the above described reaction formula 3.

The reaction of the compound (85a) with the compound (101) is carried out under reaction conditions similar to those of the reaction which converts the compound (2) into the compound (3) of the above described reaction formula 1.

In the formula, R2, X1, Y, A10, B21, R6, RA, f, R43, R44 and X2 are the same as described above, and B21′ represents a lower alkylene group, provided that the a and b of A10 are bound to Y and B21′, respectively, and the (B21′)f-CH═C moiety in the side chain (Y-A10-(B21′)f-CH═C(COOR43)(COOR44)) of the compound (90c) and the alkyl moiety in the side chain (NHCH(RA)(B21R6)) of the compound (90b) have not more than 6 carbon atoms, respectively.

The reaction of the compound (87) with the compound (88) is carried out under reaction conditions similar to those of the reaction of the compound (1f) and hydroxylamine of the above described reaction formula 3.

The reaction which converts the compound (89a) into the compound (89b) may be carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

The reaction of the compound (89b) with the compound (20) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (89b) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (89b) with the compound (21) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, Y, A10, B21′, R65, R6, B21, RA and X2 are the same as defined above, provided that the a and b of A10 are bound to the Y group and the B21′ group, respectively, and the alkyl moiety in the side chain (NHCH(RA)(B21R6)) of the compound (91b) has not more than 6 carbon atoms.

The reaction which converts the compound (86a′) into the compound (86b) may be carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

The reaction of the compound (86b) with the compound (20) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (86b) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (86b) with the compound (21) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, Y, A10, B21, B21′, R6, RA and X2 are the same as described above, provided that the a and b of A10 are bound to the Y group and the B21′ group, respectively, and the alkyl moiety in the side chain (NHCH(RA)(B21R6)) of the compound (44c) has not more than 6 carbon atoms.

The reaction which converts the compound (92a) into the compound (92b) may be carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

The reaction of the compound (92b) with the compound (20) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (92b) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (92b) with the compound (21) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, and X2 are the same as described above, R67 represents an -A10B21CN group, -A10-R59d group, -A10-T2-COOR59a group or -A group, R59d represents a lower alkyl group, A10, B21, T2 and R59a are the same as described above, and R68 represents a nitro group or a halogen atom.

The reaction of the compound (93) with the compound (94) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula, R2, R67, and X1 are the same as described above.

The reaction which converts the compound (95a) into the compound (95b) may be carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

In the formula, R2, X1, Y, A7, R6, B21, RA and X2 are the same as described above, provided that the alkyl moiety in the side chain (NHCH(RA)(B21R6)) of the compound (13b) has not more than 6 carbon atoms.

The reaction of the compound (96) with the compound (20) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (96) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (96) with the compound (21) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, Y, B21, f, i, R6, B21, A10, RA and X2 are the same as described above, and RA′ represents a hydrogen atom or a lower alkyl group, provided that the alkyl moiety in the side chain (NHCH(RA)(B21R6)) in compound (98b) has not more than 6 carbon atoms, and the a and b of A10 are bound to the Y group and the (B21)f group, respectively.

The reaction which converts the compound (97a) into the compound (97b) is carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

The reaction of the compound (97b) with the compound (20) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (97b) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (97b) with the compound (21) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R1, R2, X1, Y, A10, B21, f, RA′ and A3 are the same as described above, provided that the a and b of A10 are bound to the Y group and the (B21)f group, respectively.

The reaction which converts the compound (98d) into the compound (9′) may be carried out under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

In the formula, R1, R2, X1, Y, A3, R59, A10, B21 and f are the same as described above, T3 represents a direct bond or B7 group, and B7 represents the same as described above, provided that The a and b of A10 are bound to the Y group and the (B21)f group, respectively.

The reaction of the compound (9′) with the compound (99) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, Y, A10, R14a, R49a, R49, R49b, T, l, RA and X2 are the same as described above, provided that the CHRA moiety in the side chain (N(R14a)(CHRAR49b)) of the compound (104c) has not more than 6, the a of A10 is bound to the Y group, and the b of A10 is bound to a NR14aH group, NR14aR49a group, NR14aR49 group, or NR14a (CHRAR49b) group.

The reaction of the compound (103) with the compound (38a) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (103) with the compound (38) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (103) with the compound (38b) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, Y and A are the same as described above.

The reaction which converts the compound (105) into the compound (19a) is carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47. The compound (19a) may be used in the following reaction without isolation.

In the formula, R2, X1, Y and A10 is the same as described above, R69a represents a thiazolidinyl group which may have an oxo group as a substituent on the thiazolidine ring, R69 represents a thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, and R70 represents a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, provided that the a of A10 are bound to the Y group and the b of A10 is bound to an R69 group or R70 group.

The reaction of the compound (106a) with the compound (160) is carried out under reaction conditions similar to those of the reaction of the compound (87) with the compound (88) of the above described reaction formula 58.

The reaction which converts the compound (106) into the compound (19b) may be carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

In the formula, R2, X1, X2, A, Y1, A10, T2, R5 and R59a are the same as described above, X3 represents a halogen atom, R71 represents an R1 group (wherein R1 is the same as described above), a nitro group or a lower alkoxycarbonyl group, and R72 represents a lower alkyl group which may be substituted with a hydroxyl group, a nitro group, an amino group which may be substituted with a lower alkanoyl group, a carboxy lower alkyl group, a (B21)fC(═O)RA group (wherein B21, f and RA are the same as described above), a lower alkanoyl group, a lower alkoxy group or a hydrogen atom, provided that the a of A10 are bound to the Y1 group and the b of A10 is bound to a -T2 group or R72 group.

The reaction of the compound (94a) with the compound (107), and the reaction of the compound (94a) with the compound (107a) are carried out in an appropriate solvent and in the presence of a catalyst.

Any of the solvents used in the reaction of the compound (2) with the compound (3) of the above described reaction formula 1 may be used in this reaction.

Examples of the catalyst to be used include various metal complexes as well as various combinations of a metal complex with ligand. Examples of the metal complex include, for instance, palladium acetate (II), tetrakis(triphenylphosphine)palladium (0), tris(dibenzylideneacetone)dipalladium (0) and the like. Examples of the ligand include, for instance, R-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (R-BINAP), S-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (S-BINAP), RAC-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (RAC-BINAP), t-butylphosphine, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and the like.

The above described catalyst is appropriately used in an amount typically equimolar to the compound (94a), and preferably 1 to 5 times of the compound (94a) on a molar basis.

The above described reaction is carried out typically at about 0 to 200 C., preferably at about 0 to 150 C., and, in general, is completed in around 30 minutes to 10 hours.

Addition of molecular sieves such as Molecular Sieves 3A (MS3A) or Molecular Sieves 4A (MS4A) or a phosphorus compound such as triphenylphosphine or tri(2-furyl)phosphine makes the reaction proceed advantageously.

The reaction of the compound (94a) with the compound (108), compound (3) or compound (110) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The compound (109c), wherein R71 represents a lower alkoxycarbonyl group, may be converted into the corresponding compound (109c), wherein R71 represents a carboxy group, by hydrolyzing under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

In the formula, R1, R2, X1, X2, Y1, A10 and T2 are the same as described above, and R59c represents a hydrogen atom, a lower alkyl or a phenyl lower alkyl group, provided that the a and b of A10 are bound to a Y1 group and a -T2 group, respectively.

The reaction of the compound (2) with the compound (108′) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula, R2, X1, R5a, R5b, RA, R5c and X are the same as described above, and R73a represents a -A10-T2-COOR59 group (wherein A10, T2 and R59 are the same as described above) or an -A group (wherein A is the same as described above), provided that the a of A10 is bound to an NH group, NR5a group, N(CHRAR5b) group or NR5c group, and the b of A10 is bound to a -T2 group, and the alkyl moiety in the side chain (N(R73a)(CHRAR5b)) of the compound (68d) has not more than 6 carbon atoms.

The reaction of the compound (111) with the compound (4) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (111) with the compound (6) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (111) with the compound (5) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, Y, A10, X2, R17, B3, R74a and Rc are the same as described above, provided that the a of A10 is bound to a Y group and the b of A10 is bound to an NHR17 group or NR17B3Rc group.

The reaction of the compound (112) with the compound (113) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

In the formula, R2, X1, Y, A10, T1, l, R14, and R15 are the same as described above, provided that the a and b of A10 are bound to an Y group and a -(T1)l group, respectively.

The reaction of the compound (114) with the compound (36) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

The compound (109e), in which l is 0, may also be produced by reacting the corresponding compound (114) with the compound (36) in an appropriate solvent in the presence of a basic compound and a catalyst.

The above described reaction is carried out under reaction conditions similar to those of the reaction C described for the above described reaction formula 13.

In the formula, R2, X1, Y, R8, B21, R6, A10, T2, R59, RA and X2 are the same as described above, provided that the CHRAB21 moiety in the side chain (N(R8)(CH(RA)B21R6)) of the compound (84i) has not more than 6 carbon atoms, and the a and b of A10 are bound to a Y group and a -T2 group, respectively.

The reaction of the compound (84g) with the compound (20) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (84g) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (84g) with the compound (21) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, Y, R8a, R8b, R8c, B, R6, A10, T2, R59, RA and X2 are the same as described above, provided that the CHRA moiety in the side chain (NB(R6)(CH(RA)R8b)) of the compound (116b) has not more than 6 carbon atoms, and the a and b of A10 are bound to a Y group and a -T2 group, respectively.

The reaction of the compound (115) with the compound (23) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (115) with the compound (25) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (115) with the compound (24) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, Y, A3, R14 and R15 are the same as described above, and A15 represents a group of the formula:


wherein R73 represents a (B21)fCH(RA)(NR14R15) group, and B21, f and RA are the same as described above, provided that the (B21)fCH(RA) moiety has not more than 6 carbon atoms.

The reaction of the compound (117) with the compound (36) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, Y, A10, T2, R6, R9a and R59 are the same as described above, provided that the a and b of A10 are bound to a Y group and a -T2 group, respectively.

The reaction of the compound (69′) with the compound (66) is carried out under reaction conditions similar to those of the reaction of the compound (30) with the compound (66) of the above described reaction formula 46.

In the formula, R2, X1, Y, A10, T2, R95 and R59b are the same as described above, provided that the a and b of A10 are bound to a Y group and a -T2 group, respectively.

The reaction which converts the compound (120a) into the compound (120b) may be carried out under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

The reaction of the compound (120b) with the compound (100′) is carried out under reaction conditions similar to those of the reaction of the compound (1fff) with the compound (43) in the reaction formula 20 described above.

The compound (120a) may also be produced using a lower alkyl halide such as methyl iodide in place of the compound (100′) under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula, R1, R2, X1, Y, A10, B5, R59a and j are the same as described above, provided that the a and b of A10 are bound to a Y group and a S group, respectively.

The reaction which converts the compound (120c) into the compound (120d) may be carried out under reaction conditions similar to those of the reaction which converts the compound (1zzzz) into the compound (1aaaaa) in formula 4 described above.

In the formula, R2, X1, Y, A10, T, l, R6, X2, RA, B21 and R14a are the same as described above, and R49c represents a lower alkoxycarbonyl group, provided that the a and b of A10 are bound to a Y group and a -(T)l group, respectively.

The reaction of the compound (103) with the compound (38c) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The reaction which converts the compound (104d) into the compound (104e) is carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

The reaction of the compound (104e) with the compound (20) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (104e) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (104e) with the compound (21) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, X1, Y, A3, A10, B21, f, RA and i are the same as described above, provided that the a and b of A10 are bound to a Y group and a (B21)f group, respectively, and (B21)fC(RA) in the side chain of the compound (123a) has not more than 6 carbon atoms in total.

The reaction of the compound (121) with the compound (122) may be carried out in an appropriate solvent in the presence of an acid.

Any of the solvents, which are used in the reaction of the compound (2) with the compound (3) of the above described reaction formula 1, may be used in this reaction.

Examples of the acid used include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, and organic acids such as acetic acid, trifluoroacetic acid, and sulfonic acids including p-toluenesulfonic acid. These acids may be used singly or in a mixture of two or more. The acid is appropriately used in an amount typically at least 0.01 to 5 times, and preferably 0.01 to 2 times of the compound (121) on a molar basis. The compound (122) is appropriately used in an amount typically at least equimolar to the compound (121), and preferably 1 to 10 times of the compound (121) on a molar basis.

The above described reaction is carried out typically at 0 to 200 C., and preferably at around 0 to 150 C. and, in general, is completed in around 30 minutes to 10 hours.

In the formula, R2, X1, Y and A10 are the same as described above, and R72a represents a lower alkoxy group, provided that the a of A10 is bound to a Y group and the b of A10 is bound to a R72a group or a hydroxyl group.

The reaction which converts the compound (109f) into the compound (124) may be carried out in an appropriate solvent in the presence of an acid.

In addition to water, any solvents which are used in the reaction of the compound (2) with the compound (3) of the above described reaction formula 1 may be used in this reaction.

Examples of the acid used include mineral acids such as hydrobromic acid, hydrochloric acid, and concentrated sulfuric acid, fatty acids such as formic acid and acetic acid, organic acids such as p-toluenesulfonic acid, Lewis acids such as aluminum chloride, zinc chloride, iron chloride, tin chloride, boron trifluoride, and boron tribromide, iodides such as sodium iodide and potassium iodide, a mixture of the above described Lewis acid with the above described iodide. The acid is appropriately used in an amount typically 0.1 to 5 times, and preferably 0.5 to 3 times of the compound (109f) on a molar basis.

The above described reaction is typically carried out at 0 to 150 C., and preferably at about 0 to 100 C., and, in general, is completed in about 0.5 to 15 hours.

In the formula, R2, X1, Y, A10, B5, X2, R14, and R15 are the same as described above, and Q1 represents an oxygen atom or a sulfur atom, provided that the a and b of A10 are bound to a Y group and a -Q1 group, respectively.

The reaction of the compound (124a) with the compound (125) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula, R2, X1, Y, A10, R14a, R74a, T and 1 are the same as described above, and R74b represents a lower alkanoyl group or a lower alkoxycarbonyl group, provided that the a and b of A10 are bound to a Y group and a -(T)l group, respectively.

The reaction which converts the compound (109g) into the compound (109h) may be carried out under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

In the formula, R2, X1, Y, A10, T2, X2, R59a, B23 and R6 are the same as described above, provided that the a and b of A10 are bound to Y group and -T2 group, respectively.

The reaction of the compound (126) with the compound (34) is carried out under reaction conditions similar to those of the reaction of the compound (33) with the compound (34) in formula 43 described above.

In the formula, R2, X1, Y, R74a and A10 are the same as described above, R74c represents an amino group or an R1 group (wherein R1 is the same as described above), R75 represents a lower alkanoyl group, R76 represents a lower alkoxycarbonyl group, R77 and R78 are both lower alkoxy groups, and R79 represents a hydrogen atom or a lower alkyl group, provided that the a of A10 is bound to a Y group, and the b of A10 is bound to a R75 group, C(R79)═CHR76 group or CH(R79)CH2R76 group, and the C(R79)═CH moiety or the CH(R79)CH2 moiety has not more than 6 carbon atoms.

The reaction of the compound (128) with the compound (129) is carried out in an appropriate solvent in the presence of a basic compound.

Any of the conventional solvents which do not affect the reaction may be used. Examples of such a solvent include ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme, and diglyme, aromatic hydrocarbons such as benzene, toluene, and xylene, aliphatic hydrocarbons such as n-hexane, heptane, and cyclohexane, amines such as pyridine and N,N-dimethylaniline, aprotic polar solvents such as acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, and hexamethylphosphoric acid triamide, and alcohols such as methanol, ethanol, and isopropanol, and a mixture thereof.

Examples of the basic compound include metal sodium, metal potassium, sodium hydride, sodium amide, metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide, carbonates such as sodium carbonate, potassium carbonate, and sodium bicarbonate, metal alcoholates such as sodium methylate, sodium ethylate, and potassium tert-butoxide, alkyl and aryl lithiums or lithium amides such as methyl lithium, n-butyryl lithium, phenyl lithium, and lithium diisopropylamide, and organic bases such as pyridine, piperidine, quinoline, trimethylamine, diisopropylethylamine, N,N-dimethylaniline. These basic compounds are used singly or in a mixture of two or more. The basic compound is appropriately used in an amount typically 0.1 to 10 times, and preferably 0.5 to 5 times of the compound (128) on a molar basis.

The compound (129) is appropriately used in an amount typically at least equimolar to the compound (128), and preferably 1 to 5 times of the compound (128) on a molar basis.

The above described reaction is carried out typically at −80 to 150 C., and preferably at about −80 to 120 C. and, in general, is completed in about 0.5 to 40 hours.

When an organic base is used as the basic compound, the reaction proceeds advantageously by adding a lithium salt such as lithium chloride to the reaction system.

The reaction which converts the compound (130) into the compound (131) may be carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

In the formula, R2, X1, Y, R66 and A17 are the same as described above.

The reaction which converts the compound (28′) into the compound (64a) is carried out under reaction conditions similar to those of the reaction which converts the compound (1f) into the compound (1g) of the above described reaction formula 3.

In the formula, R2, X1, Y and A are the same as described above.

The reaction which converts the compound (64b) into the compound (26a) is carried out in an appropriate solvent in the presence of an oxidizing agent.

Examples of the solvent include water, fatty acids such as formic acid, acetic acid, trifluoroacetic acid, and propionic acid, esters such as ethyl acetate and methyl acetate, alcohols such as methanol, ethanol, and isopropanol, ethers such as dioxane, tetrahydrofuran, and diethyl ether, ketones such as acetone and methyl ethyl ketone, aromatic hydrocarbons such as benzene, toluene, chlorobenzene, and xylene, and halogenated hydrocarbons such as chloroform and dichloromethane, hexamethylphosphoric acid triamide, N,N-dimethylformamide, dimethyl sulfoxide, and pyridine, and a mixture thereof.

Examples of the oxidizing agent include peracids such as performic acid, peracetic acid, pertrifluoroacetic acid, perbenzoic acid, m-chloroperbenzoic acid, and o-carboxyperbenzoic acid, hydrogen peroxide, sodium metaperidodate, dichromic acid, dichromates such as sodium dichromate and potassium dichromate, manganese dioxide, permanganic acid, permanganates such as sodium permanganate and potassium permanganate, lead salts such as lead tetraacetate, silver oxide, and a Dess-Martin reagent (Dess-Martin periodinane). These oxidizing agents are used singly or in a mixture of two or more. The oxidizing agent is used in an amount typically at least equimolar to the compound (64b), and preferably 1 to 3 times of the compound (64b) on a molar basis.

The above described reaction is carried out typically at −10 to 100 C., and preferably at about 0 to 50 C., and is completed in about 30 minutes to 24 hours.

In the formula, R2, X1, Y, A10, B19, R18, X2, R14, R74a and R15 are the same as described above, provided that the a and b of A10 are bound to a Y group and a B19 group, respectively.

The reactions between compound (133) with the compound (134), and compound (135) with the compound (36) are carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula, A10, B3, R17a, R17b, RA, R17, Y1, Rc and X2 are the same as described above, and R80 represents a Y1H group or a OR81 group, R81 represents a protective group for the hydroxyl group, provided that the CHRA moiety in the side chain (N(B3Rc)(CHRAR17b)) of the compound (108c) has not more than 6 carbon atoms, the a of A10 is bound to a R80 group, and the b is bound to an NHB3Rc group, N(R17a)B3Rc group, N(CHRAR17b)B3Rc group or N(R17)B3Rc group.

Here, examples of the protective group for the hydroxyl group include groups, which are previously mentioned, such as a phenyl lower alkyl group, a lower alkoxy lower alkyl group, tetrahydropyranyl group, tri lower alkylsilyl group, a lower alkanoyl group, and a lower alkyl group.

The reaction of the compound (108a) with the compound (73) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (108a) with the compound (75′) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (108a) with the compound (74) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

When the reaction is carried out using the compound (74) as a starting material, wherein RA and R17b are bound with each other, together with carbon atoms bound to these groups, to form a cycloalkyl ring, and a hydride reducing agent, a cycloalkyloxytrialkylsilane such as [1-ethoxycyclopropyl]oxy]trimethylsilane may be used as a starting material in place of the compound (74) to produce the above described compound (74) in the reaction system.

In the formula, R80, A10, R17, B3, Rc, X2, and R59b are the same as described above, provided that the a of A10 is bound to a R80 group and the b is bound to a NHR17 group, N(R17) B3Rc group or N(R17)CH2CH2COOR59 group.

The reaction of the compound (108e) with the compound (113) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (108e) with the compound (137) is carried out in an appropriate solvent in the presence of an acid.

Any of the solvents used in the reaction of the compound (2) with the compound (3) of the above described reaction formula 1 may be used in this reaction.

Examples of the acid used include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, organic acids such as acetic acid, trifluoroacetic acid, and sulfonic acids including p-toluenesulfonic acid, and Lewis acids such as aluminum chloride, zinc chloride, iron chloride, tin chloride, boron tribromide, and a boron trifluoride/diethyl ether complex. These acids may be used singly or in a mixture of two or more. The acid is appropriately used in an amount typically at least 0.01 to 5 times, and preferably 0.1 to 2 times of the compound (108e) on a molar basis. The compound (137) is appropriately used in an amount typically at least equimolar to the compound (108e), and preferably 1 to 10 times of the compound (108e) on a molar basis.

The above described reaction is carried out typically at 0 to 200 C., and preferably at about 0 to 150 C., and, in general, is completed in about 30 minutes to 80 hours.

In the formula, R81 is the same as described above, R73b represents a -A10-T2-COOR59a or -A group, and A10, T2, R59a and A are the same as described above, provided that the a of A10 is bound to an OR81 group or a hydroxyl group, and the b of A10 is bound to a -T2 group.

When R81 of the material compound (138) represents a phenyl lower alkyl group, the reaction which converts the compound (138) into the compound (139) may be carried out under reaction conditions similar to those of the reduction reaction (1) (method using a catalytic hydrogen reducing agent) which is one reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

When R81 of the material compound (138) represents a tetrahydropyranyl group or tri-lower alkylsilyl group, the reaction which converts the compound (138) into the compound (139) may be carried out under reaction conditions similar to those of the hydrolysis reaction B described for above described reaction formula 9. The reaction which converts the compound (138) into the compound (139) is favorably carried out by hydrolysis using an acid. The acid is appropriately used in an amount typically 1 to 10 times, and preferably 1 to 2 times of the compound (138) on a molar basis.

When R81 of the compound (138) represents a tri-lower alkylsilyl group, the compound (138) may be treated with a fluorine compound such as tetra-n-butyl ammonium fluoride, hydrogen fluoride or cesium fluoride.

When R81 of the material compound (138) represents a lower alkoxy lower alkyl group or a lower alkyl group, the compound (138) may be treated in an appropriate solvent in the presence of an acid. Examples of the solvent include water, lower alcohols such as methanol, ethanol, and isopropanol, ethers such as dioxane, tetrahydrofuran, and diethyl ether, halogenated hydrocarbons such as dichloromethane, chloroform, and carbon tetrachloride, and polar solvents such as acetonitrile, and a mixture thereof. Examples of the acid used include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, fatty acids such as formic acid and acetic acid, sulfonic acids such as p-toluenesulfonic acid, Lewis acids such as boron trifluoride, aluminum chloride, and boron tribromide, iodides such as sodium iodide and potassium iodide, and a mixture of the above described iodide with the above described Lewis acid. The above described reaction is carried out at typically 0 to 200 C., and preferably at about room temperature to 150 C., and, in general, is completed in about 0.5 to 25 hours.

The above described hydrolysis may also be carried out using a basic compound under reaction conditions similar to those of the hydrolysis reaction B described for the above described reaction formula 9. Here, amines such as triethylamine may be used as the basic compound in addition to the basic compounds used in the hydrolysis reaction B.

When R81 of the material compound (138) represents a lower alkanoyl group, the reaction which converts the compound (138) into the compound (139) may be carried out under reaction conditions similar to those of the hydrolysis reaction B described for the above described reaction formula 9.

When R73a of the compound (138) represents a group of the formula:


a dehydration reaction takes place under the above described hydrolysis conditions, and sometimes the compound (138), wherein the corresponding R73a represents a group of the formula:


may be obtained.

In the formula, R80, A10, T2, R14 and R15 are the same as described above, provided that the a and b of A10 are bound to a R80 group and a -T2 group, respectively.

The reaction of the compound (140) with the compound (36) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, Y1, A7, R13 and A9 are the same as described above.

The reaction of the compound (141) with the compound (12) is carried out under reaction conditions similar to those of the reaction of the compound (13) with the compound (12) in formula 8 described above.

In the formula, R80, A10, B21 and f are the same as described above, provided that the alkyl moiety in the side chain ((B21)f-CH2NH2) of the compound (144) has not more than 6 carbon atoms.

The reaction which converts the compound (143) into the compound (144) may be carried out under reaction conditions similar to those of the reaction using a hydride reducing agent which is one reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R80, A10, B19, X2, R18, R14 and R15 are the same as described above, provided that the a of A10 is bound to a R80 group and the b is bound to a B19 group.

The reaction of the compound (145) with the compound (134) is carried out under reaction conditions similar to those of the reaction of the compound (133) with the compound (134) in the reaction formula 90 described above.

The reaction of the compound (146) with the compound (36) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, A10, B19, R14, R15, R80 and X2 are the same as described above, and R18a represents a lower alkyl group, provided that the a and b of A10 are bound to a R80 group and a B19 group, respectively.

The reaction of the compound (108j) with the compound (147) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

In the formula, R2, X1, X2, X3 and R6 are the same as described above, R82 represents a lower alkyl group, and R83 represents a lower alkoxy group.

The reaction of the compound (148) with the compound (149) is carried out in an appropriate solvent in the presence of a catalyst.

Any of the solvents used in the reaction of the compound (2) with the compound (3) of the above described reaction formula 1 may be used in this reaction.

Examples of the catalyst include magnesium. The catalyst is appropriately used in an amount typically at least equimolar to the compound (148), and preferably 1 to 5 times of the compound (148) on a molar basis.

The above described reaction is carried out typically at 0 to 200 C., preferably at about 0 to 150 C., and, in general, is completed in about 30 minutes to 10 hours.

In the formula, A18 represents a -A group or -A10-T2-COOR59b group, and A, A10, T2, R59b and X3 are the same as described above.

The reaction which converts the compound (150) into the compound (107′) is carried out under reaction conditions similar to those of the reaction which converts the compound (85) into the compound (7′) of the above described reaction formula 55.

In the formula, R2, X1, A10, T2 and R6 are the same as described above, provided that the a of A10 is bound to CO group, CH(OH) group or CH2, and the b is bound to a -T2 group.

The reaction which converts the compound (109a′) into the compound (151) may be carried out under reaction conditions similar to those of the reaction using a hydride reducing agent which is one reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

The reaction which converts the compound (151) into the compound (152) is carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula 47.

The reaction of the compound (152) with the compound (22) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction which converts the compound (153) into the compound (154) may be carried out under reaction conditions similar to those of hydrolysis B reaction described for the above described reaction formula 9.

In the formula, R1, R2, X1, Y, A10, B6, B7 or R59 are the same as described above, and R19a represents a lower alkanoyl group, provided that the a and b of A10 are bound to a Y group and a B6 group, respectively.

The reaction of the compound (155) with the compound (156) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, R80, A10, X2, R14 and R15 are the same as described above.

The reaction of the compound (158) with the compound (36) is carried out under similar reacting conditions as the reaction of the compound (114) with the compound (36) of the above described reaction formula 74 in which l is 0.

In the formula, R1, R2, Y, A10, R14a, h, T, l, RB, X1 and X2 are the same as described above, R85a represents a benzoyl group, R85b represents a lower alkoxy carbonyl group, a phenyl lower alkyl group, a lower alkyl group or furyl lower alkyl group, and R85c represents a hydrogen atom, a lower alkyl group, a phenyl group, phenyl lower alkyl group, a furyl group or a furyl lower alkyl group, provided that the CH(RB)R85c group of the compound (1bbbbb) has not more than 6 carbon atoms.

The reaction of the compound (1yyyy′) with the compound (160′) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (1yyyy′) with the compound (161) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

The reaction of the compound (1yyyy′) with the compound (162) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2.

In the formula, R2, B0, Y, X1, A17, R8, X2, X3 and R6 are the same as described above, R86 represents a lower alkylsulfonyl group, and R87 represents a oxygen atom or a N(R8) group.

The reaction of the compound (165) with the compound (163) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The reaction which converts the compound (165) into the compound (167) is carried out under reaction conditions similar to those of the reaction which converts the compound (85) into the compound (7′) of the above described formula 55.

The reaction of the compound (166) or the compound (167) with the compound (164) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula, R80 and A10 are the same as described above, R15′ represents the same group as (5) in R15 described above.

The reaction of the compound (168) with the compound (170) is carried out under reaction conditions similar to those of the reaction of the compound (30) with the compound (66) of the above described reaction formula 46.

In the formula, R80, A10, T, l, R14bb, R15aa, R14cc, R15bb, R26 and R27 are the same as described above.

The reaction of the compound (171) with the compound (57) is carried out under reaction conditions similar to those of the reaction of the compound (1iiii) with the compound (57) of the above described reaction formula 31.

In the formula, R1, R2, X1, Y, A10, R15′ and X2 are the same as described above, and R89 represents a lower alkyl group.

The reaction of the compound (173) with the compound (170) is carried out under reaction conditions similar to those of the reaction of the compound (30) with the compound (66) of the above described reaction formula 46.

The reaction of the compound (1ddddd) with the compound (173) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.


In the formula, R1, R2, X1, Y, X2, B3, R14 and R15 are the same as described above, and A19 represents a group of the formula:


and A20 represents a group of the formula:


wherein R3, p, R17, B3, R14 and R15 are the same as described above.

The reaction of the compound (174) with the compound (175) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula, R1, R2, X1 and Y are the same as described above, A21 represents a group of the formula:


and A22 represents a group of the formula:


wherein R3, p, R17, B3, R14 and R15 are the same as described above.

The reaction which converts the compound (1ggggg) into the compound (1hhhhh) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described reaction formula 2 in which a hydrogen reducing agent is used.

In the formula, R1, R2, X1 and Y are the same as described above,

A23 represents a group of the formula:


and A24 represents a group, of the formula:


wherein R3 and p are the same as described above.

The reaction which converts the compound (1iiiii) into the compound (1jjjjj) is carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) of the above described reaction formula

In the formula, R2, X1 and Y are the same as described above,

A25 represents a group of the formula:


and A26 represents a group of the formula:


wherein B4a represents a lower alkenylene group, B4b represents a lower alkylene group, and R3, p, R14 and R15 are the same as described above.

The reaction which converts the compound (1kkkkk) into the compound (1lllll) is carried out under reaction conditions similar to those of the reaction which converts the compound (68) into the compound (69) in the (1) method of formula 47 described above.

In the formula, R2, X1, Y, and R59b are the same as described above,

A28 represents a group of the formula:


and A27 represents a group of the formula:


wherein R3, p and R59b are the same as described above.

The reaction which converts the compound (1mmmmm) into the compound (1nnnnn) is carried out under reaction conditions similar to those of the hydrolysis B reaction described for the above described reaction formula 9.

The reaction of the compound (1nnnnn) with the compound (100′) is carried out under reaction conditions similar to those of the reaction of the compound (1fff) with the compound (43) of the above described reaction formula 20.

In the formula, R2, X1, X2 and Y are the same as described above,

A29 represents a group of the formula:


and A30 represents


wherein R90 represents a lower alkyl group which may have a hydroxyl group as a substituent, and R3, p and R59b are the same as described above.

The reaction of the compound (1ooooo) with the compound (176) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

In the formula, R2, X1, X2 and Y are the same as described above,

A31 represents a group of the formula:


and A32 represents


wherein R3, p, R59b and R89 are the same as described above.

The reaction of the compound (1qqqqq) with the compound (173) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula, R1, R2, X1, Y, A10, T, l, R90 and X2 are the same as described above.

R15″ represents the group (2), (3), (4), (5), (6), (7), (8), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (20), (21), (22), (23), (24), (25), (26), (27), (26a), (27a), (28a), (29a), (30a), (31a), (32a), (33a), (34a), (35a), (36a), or (37a), which is defined for the above described R15 described above.

The reaction of the compound (1sssss) with the compound (176) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula, R1, R2, X1, Y, A10, T and l are the same as described above,

R14AA and R15BB represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one (B12CO)t-N(R2)COB16X2 group thereon,

R14CC and R15DD represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15, except that the heterocyclic ring has at least one (B12CO)t-N(R2)COB16R91 group thereon, wherein B12, t, B16 and X2 are the same as described above,
R91 represents an imidazolyl group, and
R20′ represents a hydrogen atom, a cycloalkyl group, an amino group which may have a lower alkoxycarbonyl group as a substituent, a benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring, a lower alkyl group, a lower alkyl group which have 1 or 2 phenyls which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent and a lower alkylthio group, a phenyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a cycloalkyl lower alkyl group, a pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, an amino substituted lower alkyl group which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group, a 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a naphthyl lower alkyl group, a pyridyl lower alkyl group, a quinolyl lower alkyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group, a phenyl lower alkanoyl group, a lower alkanoyl group which may have a halogen atom as a substituent, an imidazolyl lower alkanoyl group, a lower alkoxycarbonyl lower alkyl group, a pyridyl group or a carboxy lower alkyl group.

The reaction of the compound (1uuuuu) with the compound (177) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

In the formula, X1, X2, R26, Y, A and R6 are the same as described above, and R91 represents a hydrogen atom or a lower alkyl group.

The reaction of the compound (33) with the compound (178) may also be carried out in an appropriate solvent in the presence of a basic compound and a catalyst. Examples of the inert solvent used include water, aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, 2-methoxyethanol, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, fatty acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, and hexamethylphosphoric acid triamide, and a mixture thereof.

Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and cesium carbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide, potassium phosphate, sodium phosphate, sodium hydride, potassium hydride, potassium, sodium, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, sodium n-butoxide, sodium tert-butoxide, and potassium tert-butoxide, alkylsilylamide alkali metal salts such as potassium bis(trimethylsilyl)amide, and organic bases such as pyridine, imidazole, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), and 1,4-diazabicyclo[2.2.2]octane (DABCO), and a mixture thereof.

Examples of the catalyst may include palladium compounds such as palladium acetate, bis(tributyltin)/bis(dibenzylideneacetone)palladium, copper iodide/2,2′-bipyridyl, bis(dibenzylidene-acetone)palladium, copper iodide/bis(triphenylphosphine)palladium dichloride, tris(dibenzylideneacetone)dipalladium, R-tris(dibenzylideneacetone)-dipalladium, S-tris(dibenzylideneacetone)dipalladium, palladium (II) acetate, [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium (II), and tetrakis (triphenylphosphine)palladium, compounds such as R-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (R-BINAP), S-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (S-BINAP), RAC-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (RAC-BINAP), and 2,2-bis(diphenylimidazolidinyliden), xanthene compounds such as 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, and borates such as tri-tert-butylphosphine tetrafluoroborate, and a mixture thereof.

The basic compound is appropriately used in an amount at least 0.5 times, and preferably 0.5 to 40 times of the compound (33) on a molar basis. The catalyst is appropriately used in a typical catalyst amount based on the compound (33).

The compound (178) is appropriately used in an amount at least in 0.5 times, and preferably 0.5 to 3 times of the compound (33) on a molar basis.

The above described reaction is carried out typically at room temperature to 200 C., preferably at room temperature to about 150 C., and is completed in about 0.5 to 20 hours.

In the formula, Bo, X1, R2, Y, A17, R6 and X2 are the same as described above, R92 represents a R6Z4 group or R6 group and Z4 represents a lower alkylene group.

The reaction of the compound (64) with the compound (179) may be carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula R2, X1, Y, A and R6 are the same as described above.

The method for converting the compound (30) into the compound (1bbbbbb) is to obtain a compound (1bbbbbb) by subjecting the compound (30) to diazotization and by reacting the diazonium salt thus obtained with the compound (180).

The diazotization reaction 1. may be carried out in an appropriate solvent in the presence of an acid and a diazotizing agent. Examples of the solvent used in the above described reaction include water and acetonitrile. Examples of the acid used include hydrochloric acid, hydrobromic acid, sulfuric acid, tetrafluoroboric acid, and hexafluorophosophoric acid. Examples of the diazotizing agent include metal nitrites such as sodium nitrite and potassium nitrite, lower alkyl nitrites such as t-butyl nitrite and isoamyl nitrite. The acid is appropriately used in an amount typically about 1 to 10 times of the compound (30), and preferably about 1 to 5 times of the compound (30) on a molar basis. The diazotizing agent is appropriately used in an amount typically at least about equimolar to the compound (30), and preferably 1 to 3 times of the compound (30) on a molar basis. The above described reaction is typically carried out at about 0 to 70 C., and preferably at about 0 C. to room temperature, and is completed in about a few minutes to 5 hours. The reaction 2. of the diazonium salt obtained in the reaction 1. with the compound (180) may be carried out in the similar solvent as in the reaction 1 and in the presence of a basic compound. Any of the basic compounds used in the reaction of the compound (2) with the compound (3) of the above described reaction formula 1 may be used in this reaction. The basic compound is appropriately used in an amount at least equimolar to the compound (30), and preferably 1 to 5 times of the compound (30) on a molar basis. The compound (180) is appropriately used in an amount at least equimolar to the compound (30), and preferably 1 to 5 times of the compound (30) on a molar basis. The above described reaction is carried out typically at about 0 to 70 C., preferably at about 0 C. to room temperature, and is completed in about a few minutes to 5 hours.

In the formula, X1, R8d, Y, A, R2 and R6 are the same as described above.

The reaction of the compound (30a) with the compound (181) may be carried out in an appropriate solvent in the presence of an acid and a catalyst. Examples of the inert solvent used include water, aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, 2-methoxyethanol, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, fatty acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, dimethylsulfoxide, N,N-dimethylformamide, and hexamethylphosphoric acid triamide, and a mixture thereof.

Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and cesium carbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide, sodium hydride, potassium hydride, potassium, sodium, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, sodium n-butoxide, sodium tert-butoxide, and potassium tert-butoxide, organic bases such as pyridine, imidazole, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), and 1,4-diazabicyclo[2.2.2]octane (DABCO), and a mixture thereof.

Examples of the catalyst include palladium compounds such as tetrakis(triphenylphosphine)palladium (0) and dichlorobis(triphenylphosphine)palladium (II), and copper compounds such as copper (II) acetate.

The basic compound is appropriately used in an amount at least equimolar to the compound (30a), and preferably 1 to 5 times of the compound (30a) on a molar basis. The catalyst is appropriately used in an amount 0.001 to 1 times, and preferably 0.01 to 0.5 times of the compound (30a) on a molar basis.

The compound (181) is appropriately used in an amount at least equimolar to the compound (30a), and preferably 1 to 5 times of the compound (30a) on a molar basis.

The above described reaction is carried out typically at −30 to 200 C., and preferably at 0 to 150 C. and is completed in 0.5 to about 30 hours. A molecular sieve such as Molecular Sieves 3A (MS-3A), Molecular Sieves 4A (MS-4A) or the like may be added to the reaction.

In the formula, R6, Z1, X1, R2, Y and A are the same as described above. Z4 represents a lower alkylene group.

The reaction which converts the compound (1dddddd) into the compound (1eeeeee) may be carried out in an appropriate solvent in the presence of a catalytic hydrogen reducing agent.

Examples of the solvent used include water, fatty acids such as acetic acid, alcohols such as methanol, ethanol, and isopropanol, aliphatic hydrocarbons such as n-hexane, alicyclic hydrocarbons such as cyclohexane, ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, monoglyme, diglyme, and 1,4-dioxane, esters such as methyl acetate, ethyl acetate, and butyl acetate, and aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetoamide, and N-methylpyrrolidone, and a mixture thereof.

Examples of the catalytic hydrogen reducing agent include palladium, palladium-black, palladium-carbon, palladium hydroxide-carbon, rhodium-alumina, platinum, platinum oxide, copper chromite, Raney nickel, and palladium acetate.

The above described catalytic hydrogen reducing agent is typically used in an amount 0.01 to 1 times of the compound (1dddddd) on a molar basis.

The above reaction favorably proceeds typically at about −20 to 150 C., and preferably at 0 to 100 C. and, in general, is completed in 0.5 to 20 hours. The hydrogen pressure may be applied typically at 1 to 10 atm.

In the formula, R1, R2, Y, X1, A10, T and l are the same as described above; R14II, and R15JJ represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15 except for having at least one phenyl group which has a lower alkoxycarbonyl group on the heterocyclic ring; R14EE and R15FF represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15 except for having at least one phenyl group which has a carboxy group on the heterocyclic ring; R14GG and R15HH represent a 5- to 10-membered saturated or unsaturated heterocyclic group the same as defined for the above described R14 and R15 except for having at least one phenyl group which has a carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group on the heterocyclic ring; and R93 and R94 represent a hydrogen atom, a lower alkyl group or a lower alkoxy lower alkyl group.

The reaction which converts the compound (1hhhhhh) into the compound (1ffffff) may be carried out under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

The reaction of the compound (1ffffff) with the compound (182) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

In the formula, X1, R2, Y, A, X2, k, X3, R6, B20a and d′ are the same as described above.

The reaction of the compound (30) with the compound (183) is carried out under reaction conditions similar to those of the reaction of the compound (30) with the compound (66) of the above described reaction formula 46.

The reaction which converts the compound (184) into the compound (1jjjjjj) may be carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The reaction of the compound (1jjjjjj) with the compound (185) is carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

When d′ represents 0 in the compound (185), the reaction which converts the compound (1jjjjjj) into the compound (1kkkkkk) may also be carried out in an appropriate solvent in the presence of a halogenated copper such as copper iodide, an alkylglycine such as N,N-dimethylglycine, or an alkali metal phosphate such as potassium phosphate. Any of the solvents used in the reaction of the compound (2) with the compound (3) of the above described reaction formula 1 may be used here. Halogenated copper or alkylglycine is used in a typical catalyst amount. The alkali metal phosphate is appropriately used in an amount typically equimolar to the compound (1jjjjjj), and preferably 1 to 5 times of the compound (1jjjjjj) on a molar basis. The compound (185) is used in an amount typically 0.5 to 5 times, and preferably 0.5 to 3 times of the compound (1jjjjjj) on a molar basis. The above described reaction is carried out typically at about room temperature to 200 C., preferably at about room temperature to 150 C. and is completed in about 1 to 30 hours.

In the formula, X2, R2, X1, Y, A and R6 are the same as described above.

The reaction of the compound (33) with the compound (186) is carried out under reaction conditions similar to those of the reaction of the compound (33) with the compound (178) of the above described reaction formula 118.

In the formula, X1, X2, R2, R6, Y, A, B21a and c are the same as described above.

The reaction of the compound (33) with the compound (187) is carried out under reaction conditions similar to those of the reaction of the compound (33) with the compound (178) of the above described reaction formula 118.

In the formula, R8, R2, XI, Y, A16, X2, R6 and R8b are the same as described above.

The reaction of the compound (188) with the compound (189) may be carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) by the method (d) of the formula 2 in which carboxylic acid halide is reacted with amine.

The reaction of the compound (190) with the compound (191) may be carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

In the formula, R1, R2, X1, Y and A16 are the same as described above. Xa represents a halogen atom.

The reaction which converts the compound (1oooooo) into the compound (1pppppp) may be carried out in an appropriate solvent in the presence of a catalytic hydrogenation reducing agent and a hydrogen donor such as formic acid, ammonium formate, cyclohexene, or hydrazine hydrate.

Any solvent and catalytic hydrogenation reducing agent, which are used in the reaction which converts the compound (1dddddd) into the compound (1eeeeee) of the above described reaction formula 122, may be used in the above described reaction.

The above described reaction is carried out under hydrogen atmosphere typically at about 1 atm to 20 atm, and preferably at about 1 atm to 10 atm, and at about −30 to 150 C., and preferably at about 0 to 100 C. In general, the reaction is completed in about 1 to 12 hours.

The catalytic hydrogenation reducing agent is typically used at 0.01 to 40 wt %, and preferably 0.01 to 20 wt % of the compound (1oooooo).

The hydrogen donor is typically used in an amount at least equimolar to the compound (1oooooo), and preferably 1 to 10 times of the compound (1oooooo) on a molar basis.

In the formula, A10, X2, k, X3, R80 and RB are the same as described above; R94a represents a group defined as a substituent (35), (40), (42) or (50), in which o is 1, or (67), (75) to (76), (78), (80) to (81) or (84), in which s is 0, in the case where the above described R14 and R15 form a heterocyclic ring; R94b represents a group defined as a substituent (28), (30) to (34), (36) to (39), (41), (43) to (45), (47) or (49), in which t is 1, (50), in which o is 0, (52) to (60), (62) to (66), (70), (77), (79), (82) to (83), (87), (88a) or (90a) in the case where the above described R14 and R15 form a heterocyclic ring; and R94c represents a group defined as a substituent (28), (30) to (34), (39), (41), (45), (47) or (49), in which t is 1, and (50), in which o is 0, (54) to (58), (62) to (64), (66), (70), (79) or (82) to (83) in the case where the above described R14 and R15 form a heterocyclic ring, a phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxy group and a lower alkylenedioxy group, a pyridyl group which may have, on the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxy group and a lower alkyl group which may have a hydroxyl group as a substituent, a pyrrolyl group which may have 1 to 3 lower alkyl groups as substituents, a benzoxazolyl group, a benzothiazolyl group, a furyl group, a lower alkyl group which may have a substituent selected from the group consisting of a hydroxy group and a halogen atom, a naphthyl group, a 1,2,3,4-tetrahydronaphthyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a quinolyl group, a 1,2,3,4-tetrazolyl group which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group; a thiazolyl group which may have a phenyl group as a substituent on the thiazole ring; a benzoyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom, a piperidinyl group which may have a lower alkyl group as a substituent on the piperidine ring, a 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, a 1,3,4-oxadiazolyl group which may have an oxo group as a substituent on the 1,3,4 oxadiazole ring, a cycloalkyl group, a thienyl group, or an imidazolyl group.

The reaction of the compound (192) with the compound (183) may be carried out under reaction conditions similar to those of the reaction of the compound (30) with the compound (183) of the above described reaction formula 124.

The reaction which converts the compound (193) into the compound (1qqqqqq) may be carried out under reaction conditions similar to those of the reaction which converts the compound (184) into the compound (1jjjjjj) of the above described reaction formula 124.

The reaction of the compound (1qqqqqq) with the compound (195) may be carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

When R94b of the compound (195) represents (36) to (38), (43), (44), (53), (59) to (60), (87), (88a) or (90a), the reaction of the compound (1qqqqqq) with the compound (195) may also be carried out in an appropriate solvent in the presence of a copper halide such as copper iodide, an alkylglycine such as N,N-dimethylglycine, or an alkali metal phosphate such as potassium phosphate. In the above described reaction, any of the solvents used in the reaction of the compound (2) with the compound (3) of the above described reaction formula 1 may be used. The copper halide and alkylglycine are used in a normal catalyst amount. The alkali metal phosphate is appropriately used in an amount typically at least in equimolar to the compound (1qqqqqq), and preferably 1 to 5 times of the compound (1qqqqqq) on a molar basis. The compound (195) is appropriately used in an amount typically 0.5 to 5 times, and preferably 0.5 to 3 times of the compound (1qqqqqq) on a molar basis. The above described reaction is carried out typically at room temperature to 200 C., and preferably about room temperature to 150 C., and is completed in about 1 to 30 hours.

The reaction of the compound (1qqqqqq) with the compound (194) may be carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The reaction of the compound (1qqqqqq) with the compound (196) may be carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (5) of the above described formula 2.

In the formula, X1, Y, A, R2, R6, B22a, e and X2 are the same as described above, and R10a′ represents a lower alkyl group.

The reaction of the compound (1uuuuuu) with the compound (197) may be carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described formula 2.

In the formula, X1, Y, A, R26, R6 and X2 are the same as described above. R10b′ represents a lower alkyl group.

The reaction of the compound (1wwwwww) with the compound (197a) may be carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (4) of the above described reaction formula 2.

In the formula, R1, X1, R2, Y, A10, X2, R14a and R59b are the same as described above, and R96 represents a piperazinyl group which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a phenyl lower alkyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group) and a pyridyl lower alkyl group.

The reaction of the compound (198) with the compound (199) may be carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The reaction which converts the compound (200) into the compound (201) may be carried out under reaction conditions similar to those of the hydrolysis B described for the above described reaction formula 9.

The reaction of the compound (201) with the compound (100′) is carried out under reaction conditions similar to those of the reaction of the compound (120b) with the compound (100′) of the above described reaction formula 79.

The reaction of the compound (201) with the compound (202) is carried out under reaction conditions similar to those of the reaction of the compound (1b) with the compound (6) of the above described reaction formula 2.

The compound (200) may also be produced by the method of the following reaction formula 133:


wherein R74a, R2, X1, Y, A10, R59b and X2 are the same as described above, and R14a′ represents a lower alkyl group which may have a hydroxy group as a substituent.

The reaction of the compound (200a) with the compound (203) may be carried out under reaction conditions similar to those of the reaction of the compound (2) with the compound (3) of the above described reaction formula 1.

The compound (3) may also be produced by the method of the following reaction formula 134:


wherein R80, A10, B23a, R14 and R15 are the same as described above.

The reaction which converts the compound (1081) into the compound (108m) may be carried out under reaction conditions similar to those of the reaction which converts the compound (1f) into the compound (1g) of the above described reaction formula 3.

In the formula, R1, R2, X1, Y, A10, B23a, R14 and R15 are the same as described above.

The reaction which converts the compound (1zzzzzz) into the compound (1AAAAAA) may be carried out under reaction conditions similar to those of the reaction which converts the compound (64b) into the compound (26a) of the above described reaction formula 89 described above.

Each of the target compounds obtained by the formulas shown above may be isolated and purified by separating the crude reaction product from the reaction mixture after cooling using an isolation procedure such as filtration, concentration, or extraction, and by purifying using a common purification procedure such as column chromatography or re-crystallization.

The compound of the present invention represented by the general formula (1) includes a stereoisomers and an optical isomer.

The compound of the present invention, which has a basic group, may easily form a salt with a common pharmacologically acceptable acid. Examples of such an acid include mineral acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, and phosphoric acid, and organic acids such as methanesulfonic acid, p-toluenesulfonic acid, acetic acid, citric acid, tartaric acid, maleic acid, fumaric acid, malonic acid, and lactic acid.

The compound of the present invention, which has an acidic group, may easily form a salt with a common pharmacologically acceptable basic compound. Examples of such a basic compounds include sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.

Next, medical formulations which contain the compound of the present invention as an active ingredient will be described.

The above described medical formulations, which are obtained by preparing the compound of the present invention formulated into a common pharmaceutical form, are prepared using a diluent or excipient commonly used such as a filler, expander, binder, moistener, disintegrator, surfactant, or lubricant.

Such medical formulations may be chosen from various forms according to the therapeutic objectives, and typical examples of such formulations include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, and injections (liquids, suspensions).

Carriers which are used for forming tablets may be chosen widely from the conventional ones, of which examples include excipients such as lactose, saccharose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, and crystalline cellulose, binders such as water, ethanol, propanol, simple syrup, a glucose solution, a starch solution, a gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, and polyvinylpyrrolidone, disintegrators such as dried starch, sodium arginate, agar powder, laminaran powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid ester, sodium lauryl sulfate, stearic acid monoglyceride, starch, and lactose, anti-disintegrators such as saccharose, stearine, cacao butter, and hydrogenated oil, absorbefacients such as quartenary ammonium base and sodium lauryl sulfate, wetting agents such as glycerol and starch, adsorbents such as starch, lactose, kaolin, bentonite, and colloidal silicate, and lubricants such as purified talc, stearate, boric acid powder, and polyethylene glycol.

Further, tablets may be made into conventional coated tablets, for example, sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, or double or multi-layered tablets.

Carriers which are used for forming pills may be chosen widely from the conventional ones, of which examples include excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin, and talc, binders such as gum arabic powder, tragacanth powder, gelatin, and ethanol, and disintegrators such as laminaran and agar.

Carriers which are used for forming suppositories may be chosen widely from the conventional ones, of which examples include polyethylene glycol, cacao butter, higher alcohols, esters of higher alcohols, gelatin, and semi-synthetic glycerides.

The injection preparations in liquid, emulsion and suspension forms are preferably sterilized and isotonic with the blood. Diluents which are used for forming these liquid, emulsion and suspension preparations may be chosen widely from the conventional ones, of which examples include water, ethanol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, and polyoxyethylene sorbitan fatty acid ester. In this case, the medical formulations may contain sodium chloride, glucose or glycerol enough to prepare isotonic solutions. Also, conventional solubilizers, buffers, analgestics, and the like, and, as necessary, coloring agents, preservatives, spices, flavors, sweets and the like, or other pharmaceuticals may be added.

Although the amount of the compound of the present invention included in the medical formulation is not limited and may be selected appropriately in a wide range, it is typically preferable that the medical formulation contains the compound of the present invention at 1 to 70 wt %.

The method for administration of the medical formulation of the present invention is not limited and the administration is carried out in accordance with the conditions such as forms of the medical formulation, patient's age, sex, severity of the disease and other conditions. For example, tablets, pills, liquids, suspensions, emulsions, granules and capsules are administered orally. The injection formulations are administered intravenously singly or by mixing with a conventional fluid replacement such as a glucose solution or amino acid solution, or, as necessary, administered singly and intramuscularly, intradermally, subcutaneously or intraperitoneally. The suppositories are administered into the rectum.

The dosage for the above mentioned medical formulation may be chosen appropriately according to the usage, patient's age, sex and severity of the disease and other conditions. Typically, 0.001 to 100 mg per kg body weight per day, preferably 0.001 to 50 mg per kg body weight per day, is administered once or in several times a day.

Since the above described dosage may vary in accordance with various conditions, it may be sufficient with a dosage smaller than in the above described range, or it may be necessary to administer a dosage larger than in the above described range.

The compound of the present invention has a superior effect on suppressing the production of collagen.

The compound of the present invention has lower side effects and is excellent in safety.

EXAMPLES

The present invention is explained in more detail by illustrating Reference Examples, Examples, Formulation Example and Pharmacological Test as follows.

Reference Example 1 Production of 1-(t-butoxycarbonyl)-4-(4-hydroxyphenyl)-1,2,5,6-tetrahydropyridine Step 1 Production of 1-(t-butoxycarbonyl)-4-[(4-methoxymethoxy)phenyl]-4-hydroxypiperidine

A solution of 1-bromo-4-methoxymethoxybenzene (5.43 g, 25.0 mmol) in tetrahydrofuran (THF) (100 mL) was stirred at −85 C., and a 2.46 M n-butyllithium hexane solution (10.2 mL, 25.0 mmol) was added dropwise to the stirred solution over 10 minutes. The resulting solution was stirred at the same temperature for 40 minutes. To the reaction solution was added dropwise for 10 minutes a solution of 1-(t-butoxycarbonyl)-4-piperidone (5.20 g, 26.0 mmol) in THF (30 mL). The temperature of the resulting solution was raised to −25 C. over 4 hours, and then the solution was stirred at that temperature for 2 hours. An aqueous solution of saturated ammonium chloride was then added to this solution. The reaction solution was extracted with ethyl acetate and dried over anhydrous magnesium sulfate, after which the solvent was evaporated. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=2:3, in ratio by volume; hereinafter the same), to thereby yield 7.63 g of the title compound.

Appearance: Colorless oil

1H NMR (CDCl3) δ 1.49 (9H, s), 1.73 (2H, d, J=12.0 Hz), 1.97 (2H, brs), 3.24 (2H, brs), 3.48 (3H, s), 4.00 (2H, brs), 5.17 (2H, s), 7.03 (2H, d, J=9.0 Hz), 7.39 (2H, d, J=9.0 Hz).

Step 2 Production of 1-(t-butoxycarbonyl)-4-(4-hydroxyphenyl)-1,2,5,6-tetrahydropyridine

To a solution of 1-(t-butoxycarbonyl)-4-[(4-methoxymethoxy)phenyl]-4-hydroxypiperidine (5.32 g, 15.8 mmol) in toluene (100 mL) was added p-toluenesulfonic acid monohydrate (0.56 g, 2.95 mmol), and the resulting solution was refluxed for 21 hours. The reaction solution was cooled to room temperature, and evaporated under reduced pressure. To this crude product were added ethanol (60 mL) and 2 M hydrochloric acid (40 mL, 80 mmol), and the resulting solution was stirred for 2 hours at 60 C. The reaction solution was again cooled to room temperature, and evaporated under reduced pressure. To the residue were added methanol (100 mL), triethylamine (9.0 mL, 64.6 mmol) and di-t-butyl dicarbonate (5.20 g, 23.8 mmol), and the resulting solution was stirred for 24 hours at room temperature. The solvent was evaporated under reduced pressure, after which to the residue was added 100 mL of ethyl acetate. Insoluble matter was removed by filtration, after which the filtrate was evaporated under reduced pressure. To the residue were added 1,4-dioxane (50 mL) and a 1 M aqueous solution of sodium hydroxide (50 mL, 50 mmol) and stirred for 14 hours at 60 C. To the resulting reaction solution was added at room temperature 2 M hydrochloric acid (25 mL, 50 mmol) to neutralize, and then extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated to thereby yield 4.10 g of the title compound.

Appearance: Brown amorphous

1H NMR (CDCl3) δ 1.49 (9H, s), 2.47 (2H, brs), 3.62 (2H, t, J=5.5 Hz), 4.05 (2H, brs), 5.91 (1H, brs), 6.81 (2H, d, J=9.0 Hz), 7.25 (2H, d, J=9.0 Hz).

Reference Example 2 Production of methyl 5-(4-benzylpiperazin-1-yl)-2-methoxymethoxybenzoate

To a solution of methyl 5-chloro-2-methoxymethoxybenzoate (1.45 g, 6.29 mmol) and 1-benzylpiperazine (1.66 g, 9.43 mmol) in toluene (50 mL) were added palladium acetate (28 mg, 0.126 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (157 mg, 0.252 mmol) and cesium carbonate (3.07 g, 9.43 mmol), and the resulting solution was refluxed for 3 hours. Water was added to the resulting solution, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:2), to thereby yield 400 mg of the title compound.

Appearance: Yellow oil

1H NMR (CDCl3) δ 2.59-2.62 (4H, m), 3.12-3.16 (4H, m), 3.51 (3H, s), 3.57 (2H, s), 3.88 (3H, s), 5.16 (2H, s), 7.01 (1H, dd, J=9.1 Hz, 3.1 Hz), 7.10 (1H, d, J=9.1 Hz), 7.28-7.35 (6H, m).

The following compounds were produced in the same manner as in Reference Example 2.

TABLE 1
Reference
Example
No. R101 R102 R103 1H NMR (CDCl3) δ ppm
3 CH2OCH3 H 1.27(3H, t, J=7.0Hz), 1.43- 1.48(2H, m), 1.83(2H, brd, J= 13.0Hz), 1.90(1H, m), 2.28(2H, d, J=7.0Hz), 2.66(2H, dt, J=2.5 Hz, 12.0Hz), 3.47(3H, s), 3.50(2H, brd, J=12.0Hz), 4.15(2H, q, J= 7.0Hz), 5.10(2H, s), 6.89(2H, d, J= 9.0Hz), 6.95(2H, d, J=9.0Hz).
4 CH2OCH3 H 1.27(3H, t, J=7.0Hz), 1.57- 1.75(2H, m), 1.82(1H, m), 2.00(1H, m), 2.68-2.75(2H, m), 2.93(1H, dd, J=10.0Hz, 12.0 Hz), 3.34(1H, d, J=12.0Hz), 3.48(3H, s), 3.56(1H, brd, J=10.0 Hz), 4.16(2H, q, J=7.0Hz), 5.11(2H, s), 6.91(2H, d, J=9.0 Hz), 6.96(2H, d, J=9.0Hz).
5 CH3 H 1.27(3H, t, J=7.0Hz), 1.91(2H, dq, J=3.0Hz, 13.5Hz), 2.02(2H, dd, J=13.5Hz, 3.0Hz), 2.38(1H, m), 2.69(2H, dt, J=3.0Hz, 12.0 Hz), 3.48(2H, dt, J=12.0Hz, 3.0 Hz), 3.37(3H, s), 4.16(2H, q, J= 7.0Hz), 6.83(2H, d, J=9.0Hz), 6.91(2H, d, J=9.0Hz).
6 CH2OCH3 CH3 1.27(3H, t, J=7.1Hz), 1.82- 1.99(4H, m), 2.22(3H, s), 2.33- 2.42(1H, m), 2.64-2.73(2H, m), 3.50-3.52(5H, m), 4.15(2H, q, J= 7.1Hz), 5.12(2H, s), 6.70(1H, dd, J=8.9Hz, 3.1Hz), 6.78(1H, d, J= 3.0Hz), 6.95(1H, d, J=8.7Hz).
7 CH2OCH3 OCH3 1.27(3H, t, J=7.1Hz), 1.37- 1.47(2H, m), 1.81-1.94(3H, m), 2.29(2H, d, J=6.9Hz), 2.64- 2.73(2H, m), 3.51(3H, s), 3.54(2H, brs), 3.85(3H, s), 4.15(2H, q, J= 7.1Hz), 5.13(2H, s), 6.44(1H, dd, J=8.7Hz, 2.6Hz), 6.56(1H, d, J= 2.6Hz), 7.02(1H, d, J=8.7Hz).
8 CH2OCH3 CH3 1.27(3H, t, J=7.1Hz), 1.37- 1.49(2H, m), 1.80-2.04(3H, m), 2.22(3H, s), 227(2H, d, J=6.9 Hz), 2.60-2.68(2H, m), 3.48(3H, s), 3.52(2H, brs), 4.14(2H, q, J=7.1 Hz), 5.11(2H, s), 6.69-6.79(2H, m), 6.94(1H, d, J=8.7Hz).

TABLE 2
Reference
Example
No. R104 1H NMR (CDCl3) δ ppm
 9 1.48(9H, s), 1.76-1.89(4H, m), 2.78(3H, brs), 2.81(2H, brt, J=12.0Hz), 3.71(2H, brd, J= 12.0Hz), 4.15(1H, brs), 6.96(2H, d, J=9.0 Hz), 6.98(4H, s), 8.17(2H, d, J=9.0Hz).
10 1.49(9H, s), 3.13(4H, t, J=5.0Hz), 3.60(4H, t, J=5.0Hz), 6.96-7.00(6H, m), 8.18(2H, d, J= 9.0Hz).
11 1.79(2H, m), 2.03(2H, m), 2.96(2H, m), 3.41(3H, s), 3.51(2H, m), 3.73(1H, m), 4.74(2H, s), 6.95-6.98(6H, m), 8.17(2H, d, J= 9.0Hz).
12 1.28(3H, t, J=7.0Hz), 1.90(2H, dq, J=4.0 Hz, 13.0Hz), 2.05(2H, dd, J=13.0Hz, 4.0 Hz), 2.45(1H, m), 2.82(2H, dt, J=2.5Hz, 12.0 Hz), 3.62(2H, brd, J=12.5Hz), 4.17(2H, q, J= 7.0Hz), 6.95-6.98(6H, m), 8.17(2H, d, J= 9.0Hz).
13 1.31(3H, t, J=7.0Hz), 1.83(2H, m), 2.05(2H, m), 2.96(1H, m), 3.07(1H, m), 3.46(1H, m), 3.53(1H, m), 3.60(1H, m), 4.16(2H, s), 4.24(2H, q, J=7.0Hz), 6.95-7.01(6H, m), 8.17(2H, d, J=9.0Hz).

Reference Example 14 Production of methyl 5-(4-benzylpiperazin-1-yl)-2-hydroxybenzoate

To a solution of 400 mg of methyl 5-(4-benzylpiperazin-1-yl)-2-methoxymethoxybenzoate (1.1 mmol) in 1,4-dioxane (20 mL) was added a solution of 4 N hydrogen chloride in 1,4-dioxane (4 mL, 16 mmol), and the resulting solution was stirred for 2 hours at 100 C. The resulting reaction solution was subjected to distillation under reduced pressure to obtain a residue. This residue was purified by silica gel column chromatography (dichloromethane:methanol=30:1), to thereby yield 353 mg of the title compound.

Appearance: Pale yellow powder

1H NMR (CD3OD) δ 3.29-3.40 (8H, m), 3.94 (3H, s), 4.39 (2H, s), 6.91 (1H, d, J=8.9 Hz), 7.28 (1H, dd, J=8.9 Hz, 3.0 Hz), 7.42 (1H, d, J=3.0 Hz), 7.49-7.60 (5H, m).

The following compounds were produced in the same manner as in Reference Example 14.

TABLE 3
Reference
Example
No. R105 R106 Form 1H NMR (solvent) δ ppm
15 H free (DMSO-d6) 1.20(3H, t, J=7.0Hz), 1.78(2H, brs), 1.91(2H, brs), 2.10(1H, brs), 2.34(2H, brs), 3.45(2H, brs), 3.55(2H, brs), 4.09(2H, q, J=7.0Hz), 6.88(2H, brs), 7.60(2H, brs), 10.05(1H, brs), 11.75(1H, brs).
16 H free (DMSO-d6) 1.20(3H, t, J=7.0Hz), 1.64(1H, brs), 1.93(2H, brs), 2.08(2H, brs), 3.30(1H brs), 3.45(2H, brs), 3.48(2H, brs), 4.10(2H, q, J=7.0Hz), 6.88(2H, brs), 7.66(2H, brs), 10.05(1H, brs), 12.60(1H, brs).
17 CH3 hydrochloride (DMSO-d6) 1.22(3H, t, J=7.1Hz), 2.03-2.13(4H, m), 2.14(3H, s), 2.75(1H, brs), 3.38-3.57(4H, m), 4.12(2H, q, J=7.1Hz), 6.89(1H, d, J=8.6Hz), 7.46-7.53(2H, m), 9.99(1H, brs).
18 OCH3 free (CDCl3) 1.27(3H, t, J=7.1Hz), 1.98-2.18(3H, m), 2.41-2.44(4H, m), 3.30(2H, t, J=12.0Hz), 3.66(2H, d, J=11.9Hz), 3.95(3H, s), 4.15(2H, q, J=7.1Hz), 6.26(1H, brs), 6.96-7.03(2H, m), 7.85(1H, s).
19 CH3 hydrochloride (DMSO-d6) 1.20(3H, t, J=7.1Hz), 1.87(4H, brs), 2.14(4H, brs), 2.33(2H, d, J=6.4Hz), 2.52(2H, brs), 3.44(2H, brs), 4.19(2H, q, J= 7.1Hz), 6.88(1H, d, J=8.6Hz), 7.46-7.57(2H, m), 9.98(1H, brs), 12.04(1H, brs).

Reference Example 20 Production of ethyl N-(4-hydroxyphenyl)isonipecotate

To a solution of ethyl N-(4-methoxyphenyl)-isonipecotate (2.63 g, 10 mmol) in dichloromethane (100 mL) was added a solution of 2 M boron tribromide in dichloromethane (20 mL, 40 mmol), and the resulting solution was stirred for 0.5 hours at room temperature. The resulting reaction solution was poured into ice water, then an aqueous solution of 1 M sodium hydroxide (110 mL) was added to the solution. After stirring, the resulting solution was separated. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure to thereby yield 2.43 g of the title compound.

Appearance: Yellow oil

1H NMR (CDCl3) δ 1.27 (3H, t, J=7.0 Hz), 1.91 (2H, m), 2.02 (2H, brd, J=11.5 Hz), 2.38 (1H, m), 2.68 (2H, dt, J=2.0 Hz, 11.5 Hz), 3.46 (2H, dt, J=12.0 Hz, 3.0 Hz), 4.16 (2H, q, J=7.0 Hz), 4.45 (1H, brs), 6.75 (2H, d, J=9.0 Hz), 6.86 (2H, d, J=9.0 Hz).

The following compounds were produced in the same manner as in Reference Example 20.

Reference Example 21 4-(2-Fluoro-4-nitrophenoxy)phenol

1H NMR (DMSO-d6) δ 6.80-7.10 (5H, m), 8.04 (1H, ddd, J=1.4 Hz, 2.7 Hz, 9.2 Hz), 8.29 (1H, dd, J=2.7 Hz, 10.9 Hz), 9.59 (1H, s)

Reference Example 22 1-Benzyl-3-(4-hydroxyphenyl)imidazolidin-2-one

1H NMR (DMSO-d6) δ 3.18-3.40 (2H, m), 3.61-3.80 (2H, m), 4.35 (2H, s), 6.71 (2H, d, J=8.8 Hz), 7.15-7.48 (7H, m), 9.10 (1H, s).

Reference Example 23 Production of 2-(4-hydroxyphenylamino)-1-(4-piperonylpiperazin-1-yl)ethanone

To a solution of N-(4-hydroxyphenyl)glycine (11.38 g, 68.1 mmol) in N,N-dimethylformamide (DMF) (150 mL) were added under ice cooling 1-piperonylpiperazine (15.0 g, 68.1 mmol), 1-hydroxybenzotriazole monohydrate (10.43 g, 68.1 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (15.66 g, 81.7 mmol), and the resulting solution was stirred for 30 minutes under ice cooling and for 4.5 hours at room temperature. The reaction solution was concentrated under reduced pressure. To the residue was added a saturated sodium bicarbonate solution (400 mL), and extracted with ethyl acetate (400 mL). The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, to leave the resulting product solidified in a powdered form. Ethyl acetate was added, and the resulting product was filtered off and washed with ethyl acetate, to thereby yield 18.58 g of the title compound.

Appearance: Brown powder

1H NMR (DMSO-d6) δ 2.30 (2H, brs), 2.36 (2H, brs), 3.40 (2H, s), 3.47 (4H, t, J=14.5 Hz), 4.03 (2H, d, J=7.0 Hz), 4.90 (1H, brs), 5.99 (2H, s), 6.49 (2H, d, J=8.9 Hz), 6.54 (2H, d, J=8.9 Hz), 6.75 (1H, dd, J=8.0 Hz, 1.1 Hz), 6.85 (1H, d, J=8.0 Hz), 6.87 (1H, s), 8.42 (1H, s).

The following compounds were produced in the same manner as in Reference Example 23.

Reference Example 24 6-Chloro-N-(3,4-dichlorophenyl)nicotinamide

1H NMR (CDCl3) δ 7.64 (1H, d, J=8.9 Hz), 7.72 (1H, dd, J=8.7 Hz, 2.3 Hz), 7.73 (1H, dd, J=8.3 Hz, 0.7 Hz), 8.12 (1H, d, J=2.3 Hz), 8.35 (1H, dd, J=8.3 Hz, 2.5 Hz), 8.95 (1H, dd, J=2.5 Hz, 0.7 Hz), 10.71 (1H, brs).

Reference Example 25 4-(4-Piperonylpiperazine-1-carbonyl)-1-(4-hydroxyphenyl)pyrrolidin-2-one

1H NMR (CDCl3) δ 2.43-2.45 (4H, m), 2.73-2.95 (2H, m), 3.45 (2H, s), 3.49-3.54 (4H, m), 3.65-3.72 (1H, m), 3.78-3.87 (1H, m), 4.17-4.23 (1H, m), 5.96 (2H, s), 6.71-6.80 (4H, m), 6.84-6.85 (1H, m), 7.29 (2H, d, J=8.9 Hz).

TABLE 4
Reference
Example
No. Xa1 Xa2 R107 R108 Form 1H NMR (solvent) δ ppm
26 NH CH2 H benzyl free (CDCl3) 2.46-2.48(4H, m), 3.45(2H, t, J=
5.0Hz), 3.54(2H, s), 3.68(2H, t, J=
5.0Hz), 3.82(2H, s), 6.53(2H, d, J=8.7
Hz), 6.70(2H, d, J=8.7Hz), 7.27-
7.34(5H, m).
27 CH2 CH2 H benzyl free (CDCl3) 2.30-2.33(2H, m), 2.41-
2.45(2H, m), 2.55-2.60(2H, m), 2.85-
2.91(2H, m), 3.36-3.40(2H, m), 3.52(2H,
s), 3.62-3.66(2H, m), 5.10(1H, brs),
6.74-6.77(2H, m), 7.03(2H, d, J=8.6
Hz), 7.27-7.32(5H, m).
28 CH2 CH2 H piperonyl hydrochloride (DMSO-d6) 2.56-3.47(10H, m), 4.01-
4.07(1H, m), 4.18-4.48(3H, m), 6.07(2H,
s), 6.65-6.68(2H, m), 7.00-7.03(4H, m),
7.21(1H, s), 9.18(1H, brs), 11.04(1H,
brs).
29 O CH2 H piperonyl free (CDCl3) 2.31-2.50(4H, m), 3.41(2H, s),
3.52-3.72(4H, m), 4.63(2H, s), 5.94(2H,
s), 6.25(1H, brs), 6.70(2H, d, J=9.1
Hz), 6.69-6.77(1H, m), 6.73(1H, s),
6.77(2H, d, J=9.1Hz), 6.83(1H, d, J=
0.9Hz).
30 O CH2 H benzyl free (CDCl3) 2.40-2.52(4H, m), 3.51(2H, s),
3.53-3.73(4H, m), 4.63(2H, s), 5.89(1H,
brs), 6.70(2H, d, J=9.2Hz), 6.78(2H,
d, J=9.2Hz), 7.22-7.43(5H, m).
31 CH(OH) none H benzyl free (CDCl3) 1.89-2.03(1H, m), 2.21-
2.32(1H, m), 2.32-2.57(2H, m), 3.00-
3.18(1H, m), 3.20-3.35(1H, m), 3.40(1H,
d, J=13.1Hz), 3.46(1H, d, J=13.1
Hz), 3.60-3.83(2H, m), 5.13(1H, s),
6.71(2H, d, J=8.6Hz), 7.09(2H, d, J=
8.6Hz), 7.18-7.35(5H, m).
32 none none H 3-pyridyl free (DMSO-d6) 3.18-3.35(4H, m), 3.64(4H,
brs), 6.82(2H, d, J=8.4Hz), 7.21-
7.37(4H, m), 8.02-8.03(1H, m), 8.32
(1H, d, J=2.4Hz), 9.90(1H, brs).
33 CH2 CO H CO2C(CH3)3 free (CDCl3) 1.44(9H, s), 2.93-3.15(4H, m),
3.32(2H, t, J=5.2Hz), 3.50(2H, t, J=
5.2Hz), 3.97(2H, s), 5.48(1H, brs),
6.81(2H, d, J=8.6Hz), 7.11(2H, d, J=
8.6Hz).
34 NH CH2 CH3 piperonyl free (CDCl3) 2.20(3H, s), 2.41-2.46(4H, m),
3.44(4H, brs), 3.67(2H, t, J=4.8Hz),
3.81(2H, s), 4.34(1H, brs), 4.52(1H,
brs), 5.95(2H, s), 6.37(1H, dd, J=8.4
Hz, 2.6Hz), 6.44(1H, d, J=2.8Hz),
6.64(1H, d, J=8.4Hz), 6.70-6.77(2H,
m), 6.85(1H, s).

Reference Example 35 Production of ethyl(4-hydroxy-3-methylphenylamino)acetate

Potassium carbonate (5.04 g, 36.5 mmol) was added at room temperature to a solution of 4-amino-o-cresol (3.00 g, 24.4 mmol) and ethyl bromoacetate (2.70 mL, 24.4 mmol) in DMF (30 mL). The resulting solution was stirred at room temperature for 1.5 hours. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine. The ethyl acetate layer was dried over anhydrous sodium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1), to thereby yield 5.10 g of the title compound.

Appearance: Yellow solid

1H NMR (CDCl3) δ 1.28 (3H, t, J=7.1 Hz), 2.19 (3H, s), 3.84 (2H, s), 3.95 (1H, brs), 4.22 (2H, q, J=7.1 Hz), 4.59 (1H, brs), 6.36 (1H, dd, J=8.4 Hz, 2.9 Hz), 6.44 (1H, d, J=2.9 Hz), 6.63 (1H, d, J=8.4 Hz).

The following compounds were produced in the same manner as in Reference Example 35.

Reference Example 36 Ethyl(3-hydroxyphenylamino)acetate

1H NMR (CDCl3) δ 1.30 (3H, t, J=7.1 Hz), 3.88 (2H, s), 4.25 (2H, q, J=7.1 Hz), 4.29 (1H, brs), 4.85 (1H, s), 6.08-6.10 (1H, m), 6.18-6.24 (2H, m), 7.01-7.07 (1H, m)

Reference Example 37 Benzyl(4-hydroxy-3-methoxyphenylamino)acetate

1H NMR (CDCl3) δ 3.81 (3H, s), 3.92 (2H, brs), 4.01 (1H, brs), 5.09 (1H, brs), 5.20 (2H, s), 6.11 (1H, dd, J=8.4 Hz, 2.6 Hz), 6.23 (1H, d, J=2.6 Hz), 6.76 (1H, d, J=8.4 Hz), 7.31-7.38 (5H, m).

Reference Example 38 t-Butyl[3-(4-benzyloxy-3-methylphenyl)-2-oxotetrahydropyrimidin-1-yl]acetate

1H NMR (CDCl3) δ 1.47 (9H, s), 2.04-2.21 (2H, m), 2.25 (3H, s), 3.45 (2H, t, J=5.9 Hz), 3.67 (2H, t, J=5.9 Hz), 4.04 (2H, s), 5.06 (2H, s), 6.82 (1H, d, J=8.6 Hz), 7.01 (1H, dd, J=2.6 Hz, 8.6 Hz), 7.06-7.12 (1H, m), 7.26-7.48 (5H, m).

TABLE 5
Reference
Example
No. R109 R110 R111 R112 R113 1H NMR (CDCl3) δ ppm or MS
39 CH3 CH3 H H H 1H NMR 1.30(3H, t, J=7.1Hz), 2.14(3H,
s), 2.20(3H, s), 3.87(2H, s), 4.24(2H, q, J=
7.1Hz), 4.42(1H, brs), 6.29(1H, d, J=8.6
Hz), 6.58(1H, d, J=8.6Hz).
40 F H F H H 1H NMR 1.30(3H, t, J=7.1Hz), 3.85(2H,
s), 4.25(2H, q, J=7.1Hz), 4.77(1H, s),
6.37(1H, dd, J=7.9Hz, 11.8Hz), 6.73(1H,
dd, J=7.9Hz, 11.6Hz).
41 CH3 H CH3 H H 1H NMR 1.30(3H, t, J=7.1Hz), 2.15(3H,
s), 2.19(3H, s), 3.84(1H, brs), 3.89(2H, s),
4.17(1H, s), 4.25(2H, q, J=7.1Hz),
6.28(1H, s), 6.57(1H, s).
42 H CH3 CH3 H H MS 223(M+)
43 OCH3 H H H H 1H NMR 1.29(3H, t, J=7.1Hz), 3.82(3H,
s), 3.85(2H, s), 4.23(2H, q, J=7.1Hz),
5.26(1H, brs), 6.11(1H, dd, J=8.4Hz, 2.6
Hz), 6.25(1H, d, J=2.6Hz), 6.76(1H, d, J=
8.4Hz).
44 F H H H H 1H NMR 1.30(3H, t, J=7.1Hz), 3.83(2H,
s), 4.08(1H, brs), 4.24(2H, q, J=7.1Hz),
4.62(1H, d, J=3.3Hz), 6.30-6.41(2H, m),
6.85(1H, t, J=8.9Hz).
45 H H H CH3 CH3 1H NMR 1.20(3H, t, J=7.1Hz), 1.48(6H,
s), 4.15(2H, q, J=7.1Hz), 6.60-6.69(4H,
m).
46 CH3 H H CH3 H 1H NMR 1.24(3H, t, J=7.3Hz), 1.44(3H,
d, J=6.9Hz), 2.18(3H, s), 3.80(1H, brs),
4.03(1H, q, J=6.9Hz), 4.17(2H, q, J=7.3
Hz), 4.25(1H, brs), 6.37(1H, dd, J=8.4Hz,
3.0Hz), 6.45(1H, d, J=2.8Hz), 6.62(1H,
d, J=8.4Hz).
47 H H H CH3 H 1H NMR 1.24(3H, t, J=7.1Hz), 1.44(3H,
d, J=6.7Hz), 3.88(1H, brs), 4.04(1H, q, J=
6.9Hz), 4.17(2H, q, J=7.1Hz), 4.59(1H,
brs), 6.54(2H, d, J=8.9Hz), 6.68(2H, d, J=
8.9Hz).
48 CF3 H H H H MS 263(M+)

TABLE 6
Reference
Example
No. R114 R115 R116 R117 R118 1H NMR (solvent) δ ppm or MS
49 H H H H 1H NMR (DMSO-d6) 1.18(3H, t, J= 7.1Hz), 3.89(2H, d, J=6.2 Hz), 4.11(2H, q, J=7.1Hz), 6.14(1H, t, J=6.2Hz), 6.62(2H, d, J=8.8Hz), 6.90(1H, t, J=9.0 Hz), 6.97(2H, d, J=8.8Hz), 8.03(1H, dd, J=2.6Hz, 9.0Hz), 8.24(1H, dd, J=2.6Hz, 10.9Hz).
50 F H F CH3 1H NMR (CDCl3) 1.29(3H, t, J= 7.1Hz), 3.07(3H, s), 4.03(2H, s), 4.22(2H, q, J=7.1Hz), 6.22- 6.35(2H, m), 7.15(1H, d, J=9.0 Hz), 8.49(1H, dd, J=2.8Hz, 9.0 Hz), 9.01(1H, d, J=2.8Hz).
51 F F H CH3 1H NMR (CDCl3) 1.28(3H, t, J= 7.1Hz), 3.05(3H, s), 4.06(2H, s), 4.20(2H, q, J=7.1Hz), 6.72(1H, td, J=2.2Hz, 9.0Hz), 6.90(1H, td, J=1.8Hz, 9.4Hz), 7.11(1H, d, J=9.0Hz), 8.50(1H, dd, J= 2.7Hz, 9.0Hz), 9.02(1H, d, J= 2.7Hz).
52 H H H SO2CH3 1H NMR (CDCl3) 1.31(3H, t, J= 7.1Hz), 3.17(3H, s), 4.25(2H, q, J= 7.1Hz), 4.47(2H, s), 7.09(1H, d, J=8.9Hz), 7.20(2H, d, J=8.7 Hz), 7.60(2H, d, J=8.9Hz), 8.51(1H, dd, J=9.1Hz, 2.8Hz), 9.03(1H, d, J=2.8Hz).
53 CH3 H H SO2CH3 1H NMR (CDCl3) 1.31(3H, t, J= 7.1Hz), 2.16(3H, s), 3.17(3H, s), 4.25(2H, q, J=7.1Hz), 4.46(2H, s), 7.07(1H, dd, J=9.1Hz, 0.7 Hz), 7.08(1H, d, J=7.3Hz), 7.40(1H, d, J=2.6Hz), 7.44(1H, dd, J=7.3Hz, 2.6Hz), 8.50(1H, dd, J=9.1Hz, 2.8Hz), 9.01(1H, dd, J=2.8Hz, 0.7Hz).
54 H CF3 H H C2H5 MS 291(M+)

TABLE 7
Reference
Example
No. R119 R120 R121 1H NMR (CDCl3) δ ppm
55 4-CF3Ph H H 1.30(3H, t, J=7.1Hz), 3.89(2H, d, J=4.6
Hz), 3.95(2H, s), 4.20(1H, brs), 4.25(2H, q, J=
7.1Hz), 6.62(2H, d, J=8.9Hz), 6.77(1H, d,
J=8.4Hz), 6.97(2H, d, J=8.9Hz), 7.27(2H,
d, J=7.9Hz), 7.39(1H, dd, J=8.4Hz, 2.5
Hz), 7.54(2H, d, J=7.9Hz), 8.03(1H, d, J=
2.5Hz).
56 4-CF3PhO H SO2CH3 1.30(3H, t, J=7.1Hz), 3.15(3H, s), 4.23(2H,
q, J=7.1Hz), 4.45(2H, s), 5.06(2H, s), 6.99-
7.04(3H, m), 7.16(2H, d, J=8.9Hz),
7.54(2H, d, J=8.9Hz), 7.56(2H, d, J=9.2
Hz), 7.79-7.83(1H, m), 8.23(1H, d, J=2.0
Hz).
57 4-CF3PhO CH3 SO2CH3 1.30(3H, t, J=7.1Hz), 2.19(3H, s), 3.16(3H,
s), 4.24(2H, q, J=7.1Hz), 4.44(2H, s),
5.05(2H, s), 6.96-7.07(4H, m), 7.36(1H, dd, J=
8.7Hz, 2.6Hz), 7.42(1H, d, J=2.3Hz),
7.56(2H, d, J=8.9Hz), 7.80(1H, dd, J=8.6
Hz, 2.3Hz), 8.20(1H, d, J=2.3Hz).
(Ph means a benzene ring having 1 to 4 free valences. Hereinafter Ph indicates the same meaning.)

Reference Example 58 t-Butyl(3-cyano-4-hydroxyphenylamino)acetate

MS 248 (M+).

Reference Example 59 Production of 2-[4-(2-fluoro-4-nitrophenoxy)phenoxy]-1-(4-piperonylpiperazin-1-yl)ethanone

Potassium carbonate (0.350 g, 2.53 mmol) was added to a solution of 4-(2-fluoro-4-nitrophenoxy)phenol (0.420 g, 1.69 mmol) and 1-chloroacetyl-4-piperonylpiperazine (0.500 g, 1.70 mmol) in DMF (8 mL). The resulting reaction mixture was stirred for 40 minutes at 100 C. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated, to thereby yield 0.860 of the title compound.

Appearance: Brown oil

1H NMR (CDCl3) δ 2.50-2.60 (4H, m), 3.43 (2H, s), 3.50-3.70 (4H, m), 4.71 (2H, s), 5.95 (2H, s), 6.65-6.75 (2H, m), 6.80-7.05 (6H, m), 7.94 (1H, dd, J=2.3 Hz, 9.1 Hz), 8.06 (1H, dd, J=2.3 Hz, 10.4 Hz).

The following compound was produced in the same manner as in Reference Example 59.

Reference Example 60 2-[4-(2-fluoro-4-nitrophenoxy)phenylamino]-1-(4-piperonylpiperazin-1-yl)ethanone

1H NMR (DMSO-d6) δ 2.25-2.40 (4H, m), 3.43 (2H, s), 3.45-3.50 (4H, m), 3.90 (2H, d, J=5.1 Hz), 5.75 (1H, t, J=5.1 Hz), 5.99 (2H, s), 6.70-6.75 (3H, m), 6.80-7.00 (5H, m), 8.05 (1H, ddd, J=1.4 Hz, 2.7 Hz, 10.5 Hz), 8.27 (1H, dd, J=2.7 Hz, 11.0 Hz).

Reference Example 61 Production of methyl 3-(4-benzyloxyphenylamino)-propionate

Under nitrogen, 4-benzyloxyaniline (13.0 g, 65 mmol) was dissolved by heating at 70 C., and a boron trifluoride-diethyl ether complex (0.82 mL, 6.5 mmol) was added dropwise at the same temperature to the dissolved solution. Methyl acrylate (5.85 mL, 65 mmol) was then slowly added dropwise to the resulting solution. This solution was stirred for 10 hours at 70 C. After cooling with ice, ethyl acetate was added to the reaction mixture and washed with aqueous 1 N sodium hydroxide and brine. The organic layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1), to thereby yield 17.5 g of the title compound.

Appearance: Brown powder

1H NMR (CDCl3) δ 2.60 (2H, t, J=6.4 Hz), 3.39 (2H, t, J=6.4 Hz), 3.69 (3H, s), 3.77 (1H, brs), 4.98 (2H, s), 6.58 (2H, d, J=8.9 Hz), 6.85 (2H, d, J=8.9 Hz), 7.30-7.44 (5H, m).

Reference Example 62 Production of ethyl 3-(4-Methoxyphenylamino)propionate

3-(4-hydroxyphenylamino)propionic acid (4.00 g, 20.5 mmol) was added to 48% hydrobromic acid (50 mL), and the resulting solution was stirred for 2.5 hours at 100 C. After concentration under reduced pressure, ethanol (10 mL) was added to the residue, and concentrated under reduced pressure. A saturated sodium bicarbonate solution was added to the residue, and extracted with dichloromethane. The dichloromethane layer was dried over anhydrous sodium sulfate and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1), to thereby yield 1.27 g of the title compound.

Appearance: Yellow oil

1H NMR (CDCl3) δ 1.27 (3H, t, J=7.2 Hz), 2.59 (2H, t, J=6.4 Hz), 3.38 (2H, t, J=6.4 Hz), 4.15 (2H, q, J=7.2 Hz), 6.55 (2H, d, J=8.8 Hz), 6.70 (2H, d, J=8.8 Hz).

Reference Example 63 Production of ethyl[(3-fluoro-4-hydroxyphenyl)methylamino]acetate

Ethyl(3-fluoro-4-hydroxyphenylamino)acetate (1.06 g, 5.1 mmol) was dissolved in methanol (150 mL) and the resulting solution was cooled with ice. To the resulting solution were added aqueous 37% formaldehyde (1.5 mL), sodium triacetoxyborohydride (1 g, 16 mmol) and acetic acid (0.9 mL, 15 mmol), and then stirred at room temperature under a nitrogen atmosphere for 14 hours. The solvent was evaporated under reduced pressure. Water was added to the residue, and the resulting solution was neutralized with a saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:2), to thereby yield 0.93 g of the title compound.

Appearance: Light brown oil

1H NMR (CDCl3) δ 1.24 (3H, t, J=7.1 Hz), 3.00 (3H, s), 3.98 (2H, s), 4.17 (2H, q, J=7.1 Hz), 4.68 (1H, brs), 6.31-6.52 (2H, m), 6.87 (1H, t, J=8.9 Hz).

The following compounds were produced in the same manner as in Reference Example 63.

Reference Example 64 Ethyl(methyl{4-[5-(4-trifluoromethylbenzyl)pyridin-2-yloxy]phenyl}amino)acetate

1H NMR (CDCl3) δ 1.25 (3H, t, J=7.1 Hz), 3.07 (3H, s), 3.95 (2H, s), 4.04 (2H, s), 4.18 (2H, q, J=7.1 Hz), 6.69 (2H, d, J=9.1 Hz), 6.75 (1H, d, J=8.5 Hz), 7.00 (2H, d, J=9.1 Hz), 7.27 (2H, d, J=8.1 Hz), 7.39 (1H, dd, J=8.5 Hz, 2.5 Hz), 7.54 (2H, d, J=8.1 Hz), 8.04 (1H, d, J=2.5 Hz).

Reference Example 65 Ethyl[(4-hydroxy-2-trifluoromethylphenyl)methylamino]-acetate

MS 277 (M+).

TABLE 8
Reference
Example
No. R122 R123 R124 R125 M 1H NMR (CDCl3) δ ppm
66 H H CH3 CH3 1 3.00(3H, s), 3.71(3H, s), 4.01(2H,
s), 4.55(1H, brs), 6.62(2H, d, J=
9.2Hz), 6.75(2H, d, J=9.2Hz).
67 Benzyl H CH3 CH3 2 2.51-2.57(2H, m), 2.86(3H, s),
3.56-3.62(2H, m), 3.66(3H, s),
5.00(2H, s), 6.72(2H, d, J=9.1
Hz), 6.91(2H, d, J=9.1Hz), 7.30-
7.45(5H, m).
68 H F C2H5 C2H5 1 1.18(3H, t, J=7.1Hz), 1.26(3H, t,
J=7.1Hz), 3.38(2H, q, J=7.1
Hz) 3.94(2H, s), 4.19(2H, q, J=
7.1Hz), 4.61(1H, brs), 6.30-6.35